ANSWER
The radiograph shows a nondisplaced fracture of the proximal fibular head. No other fractures are evident. There is some evidence of soft-tissue injury and edema over the tibia.

An orthopedics consultation was obtained, with the presumption that the fracture would be nonsurgically managed.         

ANSWER
The radiograph shows a nondisplaced fracture of the proximal fibular head. No other fractures are evident. There is some evidence of soft-tissue injury and edema over the tibia.

An orthopedics consultation was obtained, with the presumption that the fracture would be nonsurgically managed.         

ANSWER
The radiograph shows a nondisplaced fracture of the proximal fibular head. No other fractures are evident. There is some evidence of soft-tissue injury and edema over the tibia.

An orthopedics consultation was obtained, with the presumption that the fracture would be nonsurgically managed.         

ANSWER
The correct answer is “all of the above” (choice “d”), for reasons discussed in the next section.

DISCUSSION 
Cutaneous horn is the term given to this type of keratotic lesion, for obvious reasons. They range in size from a pinpoint to the larger lesion seen on this patient (and sometimes, even larger). The pathology report in this case confirmed the clinical impression of well-differentiated squamous cell carcinoma (SCC; choice “c”); sun exposure is the most likely causative factor, given the location and the patient’s history of sun damage.

The lesion might have been a wart (choice “a”) caused by a human papillomavirus, some of which can trigger the formation of a type of SCC. Evidence of HPV involvement is often noted in the pathology report.

When skin lesions transition from normal to sun-damaged to cancerous, they often go through an actinic keratosis (choice “b”) stage, usually as a tiny hyperkeratotic papule on the forehead, ears, nose, or other directly sun-exposed area. Some consider actinic keratoses to be a form of early SCC; more prevalent is the view that they are merely “precancerous” with the potential to develop into either a frank SCC or, less often, a basal cell carcinoma. Some actinic keratoses, left completely unmolested, can develop into tag-like lesions and then horny outward projections.

Even when cutaneous horns are found to represent SCC, they are termed well-differentiated, a descriptor meant to denote a relatively benign and nonaggressive prognosis. This is the opposite of a poorly differentiated SCC, which would be expected to behave in a more aggressive, less predictable manner.

For well-differentiated lesions, a deep shave biopsy is probably an adequate method of removal. As such, the case patient did not require re-excision. He was, however, scheduled for a return visit to check the site for the (albeit unlikely) possibility of ­recurrence.   

ANSWER
The correct answer is “all of the above” (choice “d”), for reasons discussed in the next section.

DISCUSSION 
Cutaneous horn is the term given to this type of keratotic lesion, for obvious reasons. They range in size from a pinpoint to the larger lesion seen on this patient (and sometimes, even larger). The pathology report in this case confirmed the clinical impression of well-differentiated squamous cell carcinoma (SCC; choice “c”); sun exposure is the most likely causative factor, given the location and the patient’s history of sun damage.

The lesion might have been a wart (choice “a”) caused by a human papillomavirus, some of which can trigger the formation of a type of SCC. Evidence of HPV involvement is often noted in the pathology report.

When skin lesions transition from normal to sun-damaged to cancerous, they often go through an actinic keratosis (choice “b”) stage, usually as a tiny hyperkeratotic papule on the forehead, ears, nose, or other directly sun-exposed area. Some consider actinic keratoses to be a form of early SCC; more prevalent is the view that they are merely “precancerous” with the potential to develop into either a frank SCC or, less often, a basal cell carcinoma. Some actinic keratoses, left completely unmolested, can develop into tag-like lesions and then horny outward projections.

Even when cutaneous horns are found to represent SCC, they are termed well-differentiated, a descriptor meant to denote a relatively benign and nonaggressive prognosis. This is the opposite of a poorly differentiated SCC, which would be expected to behave in a more aggressive, less predictable manner.

For well-differentiated lesions, a deep shave biopsy is probably an adequate method of removal. As such, the case patient did not require re-excision. He was, however, scheduled for a return visit to check the site for the (albeit unlikely) possibility of ­recurrence.   

ANSWER
The correct answer is “all of the above” (choice “d”), for reasons discussed in the next section.

DISCUSSION 
Cutaneous horn is the term given to this type of keratotic lesion, for obvious reasons. They range in size from a pinpoint to the larger lesion seen on this patient (and sometimes, even larger). The pathology report in this case confirmed the clinical impression of well-differentiated squamous cell carcinoma (SCC; choice “c”); sun exposure is the most likely causative factor, given the location and the patient’s history of sun damage.

The lesion might have been a wart (choice “a”) caused by a human papillomavirus, some of which can trigger the formation of a type of SCC. Evidence of HPV involvement is often noted in the pathology report.

When skin lesions transition from normal to sun-damaged to cancerous, they often go through an actinic keratosis (choice “b”) stage, usually as a tiny hyperkeratotic papule on the forehead, ears, nose, or other directly sun-exposed area. Some consider actinic keratoses to be a form of early SCC; more prevalent is the view that they are merely “precancerous” with the potential to develop into either a frank SCC or, less often, a basal cell carcinoma. Some actinic keratoses, left completely unmolested, can develop into tag-like lesions and then horny outward projections.

Even when cutaneous horns are found to represent SCC, they are termed well-differentiated, a descriptor meant to denote a relatively benign and nonaggressive prognosis. This is the opposite of a poorly differentiated SCC, which would be expected to behave in a more aggressive, less predictable manner.

For well-differentiated lesions, a deep shave biopsy is probably an adequate method of removal. As such, the case patient did not require re-excision. He was, however, scheduled for a return visit to check the site for the (albeit unlikely) possibility of ­recurrence.   

LONDON – Bivalirudin did not prove superior to unfractionated heparin in reducing the rate of major adverse cardiovascular events in two nested, open-label, randomized clinical trials involving patients presenting with acute coronary syndrome who were expected to undergo percutaneous coronary intervention, Dr. Marco Valgimigli reported.

In addition, post-PCI infusions of bivalirudin for 4 hours or longer did not reduce the rate of adverse bleeding events, compared with no infusion.

These findings add important data to the understanding of antithrombotic therapy in ACS patients undergoing invasive treatment, but they do not resolve the persistent question of which method is best for preventing thrombotic complications while limiting the risk of bleeding during and after such procedures, said Dr. Valgimigli of Erasmus University in Rotterdam.

Previous studies comparing bivalirudin, a direct thrombin inhibitor, against unfractionated heparin, an indirect thrombin inhibitor, have yielded conflicting results regarding ischemic and bleeding outcomes, so Dr. Valgimigli and his fellow investigators in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial conducted two industry-sponsored superiority trials to try to settle the question.

The findings of one of these trials were reported by Dr. Valgimigli at the annual congress of the European Society of Cardiology on Sept. 1, when the results of both were simultaneously published online (N Engl J Med. 2015 Sept 1. doi: 10.1056/NEJMoa1507854).

The MATRIX studies were conducted at 78 medical centers in Italy, the Netherlands, Spain, and Sweden. They involved 7,213 patients who presented with either ST-elevation MI or non-STEMI ACS and were expected to undergo PCI. The first trial, MATRIX Antithrombin, assessed outcomes in 3,610 of these participants who were randomly assigned to receive bivalirudin and 3,603 assigned to receive unfractionated heparin. In the second trial, MATRIX Treatment Duration, the bivalirudin group was further randomized to receive either a post-PCI bivalirudin infusion (1,799 patients) or no post-PCI infusion (1,811 patients).

MATRIX Antithrombin

At 1-month follow-up, the rate of major adverse cardiovascular events (MACEs) – a composite of death from any cause, myocardial infarction, or stroke – was no lower in the bivalirudin group (10.3%) than in the heparin group (10.9%), for a rate ratio of 0.94. Similarly, the rate of net adverse clinical events was not significantly lower with bivalirudin (11.2%) than with heparin (12.4%), for a rate ratio of 0.89.

MATRIX Treatment Duration

The primary outcome in the MATRIX Treatment Duration study – a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events at 30 days – occurred in 11.0% of patients who received post-PCI bivalirudin infusions and 11.9% of those who did not, a nonsignificant difference (rate ratio, 0.91). However, the rate of subacute definite stent thrombosis was significantly higher in the post-PCI infusion group, at 0.7%, compared with 0.2% in the group that didn’t receive post-PCI infusions (RR, 4.37).

“I believe the option to prolong or stop bivalirudin infusion after PCI remains open for clinicians, who will have to decide based on the ischemic and bleeding risk of individual patients as well as, perhaps, based on type of acute coronary syndrome, timing of loading dose, and type of oral P2Y12 inhibitors,” Dr. Valgimigli said, noting that this is in keeping with the current labeling of the drug in Europe and the United States.

The MATRIX study was sponsored by the nonprofit Italian Society of Invasive Cardiology and financially supported by the Medicines Company and Terumo Medical. Dr. Valgimigli reported ties to AstraZeneca, the Medicines Company, Terumo Medical, St. Jude Vascular, Alvimedica, Abbott Vascular, and Correvio; his associates reported ties to numerous industry sources.

Mary Ann Moon contributed to this report.

LONDON – Bivalirudin did not prove superior to unfractionated heparin in reducing the rate of major adverse cardiovascular events in two nested, open-label, randomized clinical trials involving patients presenting with acute coronary syndrome who were expected to undergo percutaneous coronary intervention, Dr. Marco Valgimigli reported.

In addition, post-PCI infusions of bivalirudin for 4 hours or longer did not reduce the rate of adverse bleeding events, compared with no infusion.

These findings add important data to the understanding of antithrombotic therapy in ACS patients undergoing invasive treatment, but they do not resolve the persistent question of which method is best for preventing thrombotic complications while limiting the risk of bleeding during and after such procedures, said Dr. Valgimigli of Erasmus University in Rotterdam.

Previous studies comparing bivalirudin, a direct thrombin inhibitor, against unfractionated heparin, an indirect thrombin inhibitor, have yielded conflicting results regarding ischemic and bleeding outcomes, so Dr. Valgimigli and his fellow investigators in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial conducted two industry-sponsored superiority trials to try to settle the question.

The findings of one of these trials were reported by Dr. Valgimigli at the annual congress of the European Society of Cardiology on Sept. 1, when the results of both were simultaneously published online (N Engl J Med. 2015 Sept 1. doi: 10.1056/NEJMoa1507854).

The MATRIX studies were conducted at 78 medical centers in Italy, the Netherlands, Spain, and Sweden. They involved 7,213 patients who presented with either ST-elevation MI or non-STEMI ACS and were expected to undergo PCI. The first trial, MATRIX Antithrombin, assessed outcomes in 3,610 of these participants who were randomly assigned to receive bivalirudin and 3,603 assigned to receive unfractionated heparin. In the second trial, MATRIX Treatment Duration, the bivalirudin group was further randomized to receive either a post-PCI bivalirudin infusion (1,799 patients) or no post-PCI infusion (1,811 patients).

MATRIX Antithrombin

At 1-month follow-up, the rate of major adverse cardiovascular events (MACEs) – a composite of death from any cause, myocardial infarction, or stroke – was no lower in the bivalirudin group (10.3%) than in the heparin group (10.9%), for a rate ratio of 0.94. Similarly, the rate of net adverse clinical events was not significantly lower with bivalirudin (11.2%) than with heparin (12.4%), for a rate ratio of 0.89.

MATRIX Treatment Duration

The primary outcome in the MATRIX Treatment Duration study – a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events at 30 days – occurred in 11.0% of patients who received post-PCI bivalirudin infusions and 11.9% of those who did not, a nonsignificant difference (rate ratio, 0.91). However, the rate of subacute definite stent thrombosis was significantly higher in the post-PCI infusion group, at 0.7%, compared with 0.2% in the group that didn’t receive post-PCI infusions (RR, 4.37).

“I believe the option to prolong or stop bivalirudin infusion after PCI remains open for clinicians, who will have to decide based on the ischemic and bleeding risk of individual patients as well as, perhaps, based on type of acute coronary syndrome, timing of loading dose, and type of oral P2Y12 inhibitors,” Dr. Valgimigli said, noting that this is in keeping with the current labeling of the drug in Europe and the United States.

The MATRIX study was sponsored by the nonprofit Italian Society of Invasive Cardiology and financially supported by the Medicines Company and Terumo Medical. Dr. Valgimigli reported ties to AstraZeneca, the Medicines Company, Terumo Medical, St. Jude Vascular, Alvimedica, Abbott Vascular, and Correvio; his associates reported ties to numerous industry sources.

Mary Ann Moon contributed to this report.

LONDON – Bivalirudin did not prove superior to unfractionated heparin in reducing the rate of major adverse cardiovascular events in two nested, open-label, randomized clinical trials involving patients presenting with acute coronary syndrome who were expected to undergo percutaneous coronary intervention, Dr. Marco Valgimigli reported.

In addition, post-PCI infusions of bivalirudin for 4 hours or longer did not reduce the rate of adverse bleeding events, compared with no infusion.

These findings add important data to the understanding of antithrombotic therapy in ACS patients undergoing invasive treatment, but they do not resolve the persistent question of which method is best for preventing thrombotic complications while limiting the risk of bleeding during and after such procedures, said Dr. Valgimigli of Erasmus University in Rotterdam.

Previous studies comparing bivalirudin, a direct thrombin inhibitor, against unfractionated heparin, an indirect thrombin inhibitor, have yielded conflicting results regarding ischemic and bleeding outcomes, so Dr. Valgimigli and his fellow investigators in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial conducted two industry-sponsored superiority trials to try to settle the question.

The findings of one of these trials were reported by Dr. Valgimigli at the annual congress of the European Society of Cardiology on Sept. 1, when the results of both were simultaneously published online (N Engl J Med. 2015 Sept 1. doi: 10.1056/NEJMoa1507854).

The MATRIX studies were conducted at 78 medical centers in Italy, the Netherlands, Spain, and Sweden. They involved 7,213 patients who presented with either ST-elevation MI or non-STEMI ACS and were expected to undergo PCI. The first trial, MATRIX Antithrombin, assessed outcomes in 3,610 of these participants who were randomly assigned to receive bivalirudin and 3,603 assigned to receive unfractionated heparin. In the second trial, MATRIX Treatment Duration, the bivalirudin group was further randomized to receive either a post-PCI bivalirudin infusion (1,799 patients) or no post-PCI infusion (1,811 patients).

MATRIX Antithrombin

At 1-month follow-up, the rate of major adverse cardiovascular events (MACEs) – a composite of death from any cause, myocardial infarction, or stroke – was no lower in the bivalirudin group (10.3%) than in the heparin group (10.9%), for a rate ratio of 0.94. Similarly, the rate of net adverse clinical events was not significantly lower with bivalirudin (11.2%) than with heparin (12.4%), for a rate ratio of 0.89.

MATRIX Treatment Duration

The primary outcome in the MATRIX Treatment Duration study – a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events at 30 days – occurred in 11.0% of patients who received post-PCI bivalirudin infusions and 11.9% of those who did not, a nonsignificant difference (rate ratio, 0.91). However, the rate of subacute definite stent thrombosis was significantly higher in the post-PCI infusion group, at 0.7%, compared with 0.2% in the group that didn’t receive post-PCI infusions (RR, 4.37).

“I believe the option to prolong or stop bivalirudin infusion after PCI remains open for clinicians, who will have to decide based on the ischemic and bleeding risk of individual patients as well as, perhaps, based on type of acute coronary syndrome, timing of loading dose, and type of oral P2Y12 inhibitors,” Dr. Valgimigli said, noting that this is in keeping with the current labeling of the drug in Europe and the United States.

The MATRIX study was sponsored by the nonprofit Italian Society of Invasive Cardiology and financially supported by the Medicines Company and Terumo Medical. Dr. Valgimigli reported ties to AstraZeneca, the Medicines Company, Terumo Medical, St. Jude Vascular, Alvimedica, Abbott Vascular, and Correvio; his associates reported ties to numerous industry sources.

Mary Ann Moon contributed to this report.

1. A 30-year-old woman complained of drainage from her ear for the past three months. She admitted that her hearing was diminished in that ear. She had a history of recurrent ear infections since childhood.

Photo courtesy of Vladimir Zlinsky, MD, in Roy F. Sullivan, PhD. Audiology Forum: video otoscopy, www.rcsullivan.com. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Cholesteatoma, similar to an epidermal inclusion cyst in the skin, produces keratinaceous material that fills the middle ear, causing hearing loss and otorrhea.

For more information, see “Diminished hearing.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

2. A 2-year-old child was brought for a well-child exam two months after an episode of acute otitis media. He appeared healthy and was meeting all of his developmental milestones. An otoscopic examination revealed air-fluid levels in the right ear.

Photo courtesy of Frank Miller, MD. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Otitis media with effusion, which is a characterized by fluid in the middle ear in a patient without signs or symptoms of an acute ear infection. The most common problem, present in more than half of patients, is mild hearing loss. This is usually identified when parents express concern regarding their child’s behavior, performance at school, or language development. The absence of signs and symptoms of acute illness assists in differentiating OME from AOM.

For more information, see “Air-fluid levels in ear.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

3. A 15-month-old boy was brought in with a two-day history of fever, irritability, and frequent tugging on his left ear. The week before, he had nasal congestion, cough, and rhinorrhea. On otoscopy, his left tympanic membrane (TM) appeared erythematous, cloudy, and bulging. The TM failed to move on pneumatic otoscopy.

Photo courtesy of William Clark, MD. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Acute otitis media, which is characterized by middle-ear effusion in a patient with signs and symptoms of acute illness (eg, fever, irritability, otalgia).

For more information, see “Ear pain in baby.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

4. A 72-year-old man sought treatment for an earache in his left ear. He said that the pain began when he got a new “in the canal” hearing aid for his left ear a month earlier.

Photo courtesy of Dr. Roy F. Sullivan. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Acute otitis externa, secondary to ear canal damage done by using the new hearing aid, caused the viscous purulent discharge and narrowing of the ear canal.

For more information, see “Earache.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

5. Parents brought their 3-year-old daughter to an urgent care facility because she had been crying all day. The child was irritable, had scant otorrhea, and had been pulling on her right ear.

Photo courtesy of William Clark, MD. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Otoscopy revealed an erythematous, swollen external auditory canal and a foreign object. The parents reported that their child had been playing with a toy beaded necklace when she started crying. The patient was referred to an otolaryngologist, who removed the bead using an operating microscope for visualization. She evaluated the child for a co-existing otitis externa and decided that the external canal was markedly inflamed and probably infected.

For more information, see “Object in ear.” J Fam Pract. 2013.

1. A 30-year-old woman complained of drainage from her ear for the past three months. She admitted that her hearing was diminished in that ear. She had a history of recurrent ear infections since childhood.

Photo courtesy of Vladimir Zlinsky, MD, in Roy F. Sullivan, PhD. Audiology Forum: video otoscopy, www.rcsullivan.com. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Cholesteatoma, similar to an epidermal inclusion cyst in the skin, produces keratinaceous material that fills the middle ear, causing hearing loss and otorrhea.

For more information, see “Diminished hearing.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

2. A 2-year-old child was brought for a well-child exam two months after an episode of acute otitis media. He appeared healthy and was meeting all of his developmental milestones. An otoscopic examination revealed air-fluid levels in the right ear.

Photo courtesy of Frank Miller, MD. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Otitis media with effusion, which is a characterized by fluid in the middle ear in a patient without signs or symptoms of an acute ear infection. The most common problem, present in more than half of patients, is mild hearing loss. This is usually identified when parents express concern regarding their child’s behavior, performance at school, or language development. The absence of signs and symptoms of acute illness assists in differentiating OME from AOM.

For more information, see “Air-fluid levels in ear.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

3. A 15-month-old boy was brought in with a two-day history of fever, irritability, and frequent tugging on his left ear. The week before, he had nasal congestion, cough, and rhinorrhea. On otoscopy, his left tympanic membrane (TM) appeared erythematous, cloudy, and bulging. The TM failed to move on pneumatic otoscopy.

Photo courtesy of William Clark, MD. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Acute otitis media, which is characterized by middle-ear effusion in a patient with signs and symptoms of acute illness (eg, fever, irritability, otalgia).

For more information, see “Ear pain in baby.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

4. A 72-year-old man sought treatment for an earache in his left ear. He said that the pain began when he got a new “in the canal” hearing aid for his left ear a month earlier.

Photo courtesy of Dr. Roy F. Sullivan. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Acute otitis externa, secondary to ear canal damage done by using the new hearing aid, caused the viscous purulent discharge and narrowing of the ear canal.

For more information, see “Earache.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

5. Parents brought their 3-year-old daughter to an urgent care facility because she had been crying all day. The child was irritable, had scant otorrhea, and had been pulling on her right ear.

Photo courtesy of William Clark, MD. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Otoscopy revealed an erythematous, swollen external auditory canal and a foreign object. The parents reported that their child had been playing with a toy beaded necklace when she started crying. The patient was referred to an otolaryngologist, who removed the bead using an operating microscope for visualization. She evaluated the child for a co-existing otitis externa and decided that the external canal was markedly inflamed and probably infected.

For more information, see “Object in ear.” J Fam Pract. 2013.

1. A 30-year-old woman complained of drainage from her ear for the past three months. She admitted that her hearing was diminished in that ear. She had a history of recurrent ear infections since childhood.

Photo courtesy of Vladimir Zlinsky, MD, in Roy F. Sullivan, PhD. Audiology Forum: video otoscopy, www.rcsullivan.com. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Cholesteatoma, similar to an epidermal inclusion cyst in the skin, produces keratinaceous material that fills the middle ear, causing hearing loss and otorrhea.

For more information, see “Diminished hearing.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

2. A 2-year-old child was brought for a well-child exam two months after an episode of acute otitis media. He appeared healthy and was meeting all of his developmental milestones. An otoscopic examination revealed air-fluid levels in the right ear.

Photo courtesy of Frank Miller, MD. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Otitis media with effusion, which is a characterized by fluid in the middle ear in a patient without signs or symptoms of an acute ear infection. The most common problem, present in more than half of patients, is mild hearing loss. This is usually identified when parents express concern regarding their child’s behavior, performance at school, or language development. The absence of signs and symptoms of acute illness assists in differentiating OME from AOM.

For more information, see “Air-fluid levels in ear.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

3. A 15-month-old boy was brought in with a two-day history of fever, irritability, and frequent tugging on his left ear. The week before, he had nasal congestion, cough, and rhinorrhea. On otoscopy, his left tympanic membrane (TM) appeared erythematous, cloudy, and bulging. The TM failed to move on pneumatic otoscopy.

Photo courtesy of William Clark, MD. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Acute otitis media, which is characterized by middle-ear effusion in a patient with signs and symptoms of acute illness (eg, fever, irritability, otalgia).

For more information, see “Ear pain in baby.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

4. A 72-year-old man sought treatment for an earache in his left ear. He said that the pain began when he got a new “in the canal” hearing aid for his left ear a month earlier.

Photo courtesy of Dr. Roy F. Sullivan. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Acute otitis externa, secondary to ear canal damage done by using the new hearing aid, caused the viscous purulent discharge and narrowing of the ear canal.

For more information, see “Earache.” J Fam Pract. 2013.

For the next photograph, proceed to the next page >>

5. Parents brought their 3-year-old daughter to an urgent care facility because she had been crying all day. The child was irritable, had scant otorrhea, and had been pulling on her right ear.

Photo courtesy of William Clark, MD. Reprinted from The Color Atlas of Family Medicine. 2nd ed.

Diagnosis: Otoscopy revealed an erythematous, swollen external auditory canal and a foreign object. The parents reported that their child had been playing with a toy beaded necklace when she started crying. The patient was referred to an otolaryngologist, who removed the bead using an operating microscope for visualization. She evaluated the child for a co-existing otitis externa and decided that the external canal was markedly inflamed and probably infected.

For more information, see “Object in ear.” J Fam Pract. 2013.

There’s a high incidence of sleep-wake disturbances among patients with dementia, which can lead to institutionalization. Although research has yet to provide a definitive answer about whether circadian-active light can benefit patients with dementia, a Veterans Affairs pilot study shows promising results. To read the full article, go to Federal Practitioner: http://www.fedprac.com/specialty-focus/sleep-disorders/article/using-light-to-manage-sleep-wake-issues-in-patients-with-dementia/0bfe5c444b4ef312595c55c2585d8e60.html.

There’s a high incidence of sleep-wake disturbances among patients with dementia, which can lead to institutionalization. Although research has yet to provide a definitive answer about whether circadian-active light can benefit patients with dementia, a Veterans Affairs pilot study shows promising results. To read the full article, go to Federal Practitioner: http://www.fedprac.com/specialty-focus/sleep-disorders/article/using-light-to-manage-sleep-wake-issues-in-patients-with-dementia/0bfe5c444b4ef312595c55c2585d8e60.html.

There’s a high incidence of sleep-wake disturbances among patients with dementia, which can lead to institutionalization. Although research has yet to provide a definitive answer about whether circadian-active light can benefit patients with dementia, a Veterans Affairs pilot study shows promising results. To read the full article, go to Federal Practitioner: http://www.fedprac.com/specialty-focus/sleep-disorders/article/using-light-to-manage-sleep-wake-issues-in-patients-with-dementia/0bfe5c444b4ef312595c55c2585d8e60.html.

Immunization against hepatitis A and B is of great importance for patients with hepatitis C because concomitant infections are damaging to the liver. Vaccination offers the best protection against hepatitis A and B, particularly among high-risk populations, such as homeless individuals and intravenous drug users. A retrospective study of the medical records of 284 veterans who were receiving treatment for addictive disorders found that most patients (88%) who began an accelerated dosing program for hepatitis A and B vaccination received at least the first 3 injections of the series, thus possibly conferring substantial immunity to hepatitis A and B. To read the full article, go to Federal Practitioner: http://www.fedprac.com/specialty-focus/vaccines/article/accelerated-hepatitis-a-and-b-immunization-in-a-substance-abuse-treatment-program/4beb502484ad80699be3a086fa2e2017.html.

Immunization against hepatitis A and B is of great importance for patients with hepatitis C because concomitant infections are damaging to the liver. Vaccination offers the best protection against hepatitis A and B, particularly among high-risk populations, such as homeless individuals and intravenous drug users. A retrospective study of the medical records of 284 veterans who were receiving treatment for addictive disorders found that most patients (88%) who began an accelerated dosing program for hepatitis A and B vaccination received at least the first 3 injections of the series, thus possibly conferring substantial immunity to hepatitis A and B. To read the full article, go to Federal Practitioner: http://www.fedprac.com/specialty-focus/vaccines/article/accelerated-hepatitis-a-and-b-immunization-in-a-substance-abuse-treatment-program/4beb502484ad80699be3a086fa2e2017.html.

Immunization against hepatitis A and B is of great importance for patients with hepatitis C because concomitant infections are damaging to the liver. Vaccination offers the best protection against hepatitis A and B, particularly among high-risk populations, such as homeless individuals and intravenous drug users. A retrospective study of the medical records of 284 veterans who were receiving treatment for addictive disorders found that most patients (88%) who began an accelerated dosing program for hepatitis A and B vaccination received at least the first 3 injections of the series, thus possibly conferring substantial immunity to hepatitis A and B. To read the full article, go to Federal Practitioner: http://www.fedprac.com/specialty-focus/vaccines/article/accelerated-hepatitis-a-and-b-immunization-in-a-substance-abuse-treatment-program/4beb502484ad80699be3a086fa2e2017.html.

Q)  I am getting calls from patients saying they heard a “stomach medicine” would hurt their kidneys. What is the basis, and how should I respond?

Emerging evidence is suggestive of a causal association between proton pump inhibitor (PPI) use and acute kidney injury/interstitial nephritis. Acute kidney injury is defined as either a decrease in urine output to less than 0.5 mL/kg/h for six hours, a rise in serum creatinine of 0.3 mg/dL or more within 48 hours, or an increase in creatinine of 50% or more above baseline within a week. Acute interstitial nephritis is often definitively diagnosed by renal biopsy, with findings of acute inflammatory cells, interstitial edema, and infiltration. Medications are the most common etiology for acute interstitial nephritis and account for more than 75% of cases.⁵

According to results published in the American Journal of Kidney Diseases, a retrospective study of 133 biopsy-proven cases of acute interstitial nephritis found 70% were associated with medication use. Of these, 14% were linked to use of a PPI (other drug culprits included antibiotics and NSAIDs, responsible for 49% and 11% of cases, respectively). Overall, omeprazole was the top drug cause, at 12%.⁶

In a nested case-control study of 572,661 subjects (mean age, 65.4) taking either lansoprazole, omeprazole, or pantoprazole, 46 definite cases and 26 probable cases of first-time acute interstitial nephritis were identified. Omeprazole was the most commonly dispensed PPI in this study. The crude incidence rate per 100,000 person-years for current use of a PPI was 11.98 and for past use, 1.68.⁷

Another nested case-control study of 184,480 subjects (ages 18 and older) reported 854 ­cases of acute kidney injury, with a positive association between use of a PPI and development of renal disease, even after controlling for confounding factors (P < .0001). Of note, no significant relationship was found between acute renal injury and use of H₂ blocker therapy.⁸—CAS 

Cynthia A. Smith, DNP, APRN, FNP-BC
Renal Consultants PLLC, South Charleston, West Virginia

REFERENCES
1. Velazquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993;119:296-301.
2. Horn JR, Hansten PD. Trimethoprim and potassium-sparing drugs: a risk for hyperkalemia. www.pharmacytimes.com/publications/issue/2011/February2011/DrugInteractions-0211. Accessed August 24, 2015.
3. Medina I, Mills J, Leoung G, et al. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990;323:776-782.
4. Fralick M, Macdonald EM, Gomes T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ. 2014;349:g6196.
5. Gilbert SJ, Weiner DE, Gipson DS, et al. National Kidney Foundation’s Primer on Kidney Diseases. Philadelphia, PA: Elsevier; 2014.
6. Muriithi AK, Leung N, Valeri AM, et al. Biopsy-proven acute interstitial nephritis, 1993-2011: a case series. Am J Kidney Dis. 2014;64(4):558-566.
7. Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86(4):837-844.
8. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study.  BMC Nephrology. 2013;14:150.

Q)  I am getting calls from patients saying they heard a “stomach medicine” would hurt their kidneys. What is the basis, and how should I respond?

Emerging evidence is suggestive of a causal association between proton pump inhibitor (PPI) use and acute kidney injury/interstitial nephritis. Acute kidney injury is defined as either a decrease in urine output to less than 0.5 mL/kg/h for six hours, a rise in serum creatinine of 0.3 mg/dL or more within 48 hours, or an increase in creatinine of 50% or more above baseline within a week. Acute interstitial nephritis is often definitively diagnosed by renal biopsy, with findings of acute inflammatory cells, interstitial edema, and infiltration. Medications are the most common etiology for acute interstitial nephritis and account for more than 75% of cases.⁵

According to results published in the American Journal of Kidney Diseases, a retrospective study of 133 biopsy-proven cases of acute interstitial nephritis found 70% were associated with medication use. Of these, 14% were linked to use of a PPI (other drug culprits included antibiotics and NSAIDs, responsible for 49% and 11% of cases, respectively). Overall, omeprazole was the top drug cause, at 12%.⁶

In a nested case-control study of 572,661 subjects (mean age, 65.4) taking either lansoprazole, omeprazole, or pantoprazole, 46 definite cases and 26 probable cases of first-time acute interstitial nephritis were identified. Omeprazole was the most commonly dispensed PPI in this study. The crude incidence rate per 100,000 person-years for current use of a PPI was 11.98 and for past use, 1.68.⁷

Another nested case-control study of 184,480 subjects (ages 18 and older) reported 854 ­cases of acute kidney injury, with a positive association between use of a PPI and development of renal disease, even after controlling for confounding factors (P < .0001). Of note, no significant relationship was found between acute renal injury and use of H₂ blocker therapy.⁸—CAS 

Cynthia A. Smith, DNP, APRN, FNP-BC
Renal Consultants PLLC, South Charleston, West Virginia

REFERENCES
1. Velazquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993;119:296-301.
2. Horn JR, Hansten PD. Trimethoprim and potassium-sparing drugs: a risk for hyperkalemia. www.pharmacytimes.com/publications/issue/2011/February2011/DrugInteractions-0211. Accessed August 24, 2015.
3. Medina I, Mills J, Leoung G, et al. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990;323:776-782.
4. Fralick M, Macdonald EM, Gomes T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ. 2014;349:g6196.
5. Gilbert SJ, Weiner DE, Gipson DS, et al. National Kidney Foundation’s Primer on Kidney Diseases. Philadelphia, PA: Elsevier; 2014.
6. Muriithi AK, Leung N, Valeri AM, et al. Biopsy-proven acute interstitial nephritis, 1993-2011: a case series. Am J Kidney Dis. 2014;64(4):558-566.
7. Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86(4):837-844.
8. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study.  BMC Nephrology. 2013;14:150.

Q)  I am getting calls from patients saying they heard a “stomach medicine” would hurt their kidneys. What is the basis, and how should I respond?

Emerging evidence is suggestive of a causal association between proton pump inhibitor (PPI) use and acute kidney injury/interstitial nephritis. Acute kidney injury is defined as either a decrease in urine output to less than 0.5 mL/kg/h for six hours, a rise in serum creatinine of 0.3 mg/dL or more within 48 hours, or an increase in creatinine of 50% or more above baseline within a week. Acute interstitial nephritis is often definitively diagnosed by renal biopsy, with findings of acute inflammatory cells, interstitial edema, and infiltration. Medications are the most common etiology for acute interstitial nephritis and account for more than 75% of cases.⁵

According to results published in the American Journal of Kidney Diseases, a retrospective study of 133 biopsy-proven cases of acute interstitial nephritis found 70% were associated with medication use. Of these, 14% were linked to use of a PPI (other drug culprits included antibiotics and NSAIDs, responsible for 49% and 11% of cases, respectively). Overall, omeprazole was the top drug cause, at 12%.⁶

In a nested case-control study of 572,661 subjects (mean age, 65.4) taking either lansoprazole, omeprazole, or pantoprazole, 46 definite cases and 26 probable cases of first-time acute interstitial nephritis were identified. Omeprazole was the most commonly dispensed PPI in this study. The crude incidence rate per 100,000 person-years for current use of a PPI was 11.98 and for past use, 1.68.⁷

Another nested case-control study of 184,480 subjects (ages 18 and older) reported 854 ­cases of acute kidney injury, with a positive association between use of a PPI and development of renal disease, even after controlling for confounding factors (P < .0001). Of note, no significant relationship was found between acute renal injury and use of H₂ blocker therapy.⁸—CAS 

Cynthia A. Smith, DNP, APRN, FNP-BC
Renal Consultants PLLC, South Charleston, West Virginia

REFERENCES
1. Velazquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993;119:296-301.
2. Horn JR, Hansten PD. Trimethoprim and potassium-sparing drugs: a risk for hyperkalemia. www.pharmacytimes.com/publications/issue/2011/February2011/DrugInteractions-0211. Accessed August 24, 2015.
3. Medina I, Mills J, Leoung G, et al. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990;323:776-782.
4. Fralick M, Macdonald EM, Gomes T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ. 2014;349:g6196.
5. Gilbert SJ, Weiner DE, Gipson DS, et al. National Kidney Foundation’s Primer on Kidney Diseases. Philadelphia, PA: Elsevier; 2014.
6. Muriithi AK, Leung N, Valeri AM, et al. Biopsy-proven acute interstitial nephritis, 1993-2011: a case series. Am J Kidney Dis. 2014;64(4):558-566.
7. Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86(4):837-844.
8. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study.  BMC Nephrology. 2013;14:150.

With older women in the United States about 4 times more likely than their male counterparts to develop osteoporosis,^1,2 physicians often fail to screen for—or to treat—low bone mass in men. There are plenty of reasons why they should.

First and foremost: Osteoporosis is a leading cause of morbidity and mortality in the elderly.³ An estimated 8.8 million American men suffer from osteoporosis or osteopenia.³ And, although only about 20% of osteoporosis patients are male, men sustain between 30% and 40% of osteoporotic fractures.^1,2 What’s more, hip fracture in men has a mortality rate of up to 37.5%—2 to 3 times higher than that of women with hip fracture.^4,5

Clearly, then, it is crucial to be aware of the risks of osteoporosis faced by both men and women as they age. Here’s a look at what to consider, when to screen, and how to treat male patients who have, or are at risk for, osteoporosis.

Which men are at risk? 

The incidence of fractures secondary to osteoporosis varies with race/ethnicity and geography. The highest rates worldwide occur in Scandinavia and among Caucasians in the United States; black, Asian, and Hispanic populations have the lowest rates.^6,7 As with women, the risk of osteoporotic fracture in men increases with age. However, the peak incidence of fracture occurs about 10 years later in men than in women, starting at about age 70.⁸ Approximately 13% of white men older than 50 years will experience at least one osteoporotic fracture.⁹

There are 2 main types of osteoporosis: primary and secondary. Up to 40% of osteoporosis in men is primary,⁴ with bone loss due either to age (senile osteoporosis) or to an unknown cause (idiopathic osteoporosis).¹⁰ For men 70 years or older, osteoporosis is assumed to be age related. Idiopathic osteoporosis is diagnosed only in men younger than 70 who have no obvious secondary cause.¹⁰ There are numerous secondary causes, however, and most men with bone loss have at least one.⁴

Common secondary causes: Lifestyle, medical conditions, and meds

The most common causes of secondary osteoporosis in men are exposure to glucocorticoids, primary or secondary hypogonadism (low testosterone), diabetes, alcohol abuse, smoking, gastrointestinal (GI) disease, hypercalciuria, low body weight (body mass index <20 kg/m2), and immobility (TABLE 1).^4,5,8,10

Chronic use of corticosteroids, often used to treat chronic obstructive pulmonary disease (COPD), asthma, and rheumatoid arthritis, directly affects the bone, decreasing skeletal muscle, increasing immobility, and reducing intestinal absorption of calcium as well as serum testosterone levels.¹⁰ Men with androgen deficiency (which may be due to androgen deprivation therapy to treat prostate cancer) or chronic use of opioids are also at increased risk.^4,5,10-12

Diagnostic screening and criteria

The World Health Organization has established diagnostic criteria for osteoporosis using bone mineral density (BMD), reported as both T-scores and Z-scores as measured on dual-energy x-ray absorptiometry (DEXA) scan.¹³ The T-score represents the number of standard deviations above or below the mean BMD for young adults, matched for sex and race, but not age. It classifies individuals into 3 categories: normal; low (osteopenia), with a T-score between -1 and -2.5; and osteoporosis (T-score ≤-2.5).^4,14 The Z-score indicates the number of standard deviations above or below the mean for age, as well as sex and race. A Z-score of ≤-2.0 is below the expected range, indicating an increased likelihood of a secondary form of osteoporosis.¹⁴

Which men to screen?

The US Preventive Services Task Force has concluded that evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men. It therefore makes no recommendation to screen men who don't have evidence of previous fractures or secondary causes of osteoporosis.¹⁵

Other organizations agree that there is insufficient evidence to recommend routine screening for men without known osteoporotic fractures or secondary causes for osteoporosis. There are, however, some guidelines that are useful in clinical practice.

The most common causes of secondary osteoporosis in men include exposure to glucocorticoids, primary or secondary hypogonadism, diabetes, alcohol abuse, and smoking.

The Endocrine Society, American College of Physicians (ACP), and National Osteoporosis Foundation (NOF) recommend screening men ages 70 years or older, and men ages 50 to 69 who have risk factors for fracture and/or a history of fracture sustained after age 50.^5,16,17 (See “Did you know?”)^{1,2,4,5,9-12,16,17} Prior to screening, it is important to do a complete medical history and physical examination.

Screening considerations. The Endocrine Society, ACP, and NOF recommend a DEXA scan of the spine and hip for men who are at increased risk for osteoporosis and have no contraindications to drug therapy.^5,16,17 In patients who have degenerative changes of the spine and hip that would likely obscure DEXA outcomes, a scan of the radius may provide a more accurate assessment of bone status. Men receiving androgen deprivation therapy for prostate cancer will have a greater decline of bone density in the radius than in the hip or spine and are therefore ideal candidates for DEXA of the forearm, as well.^5,11 Keep in mind, however, that no studies have looked at how well, or whether, men with osteoporosis measured only in the radius respond to treatment.⁵

A DEXA scan is not always widely available, nor is it a perfect predictor of fracture risk. In addition, it is not always cost effective. For some patients, the use of a validated clinical predictive tool is preferable as an initial option.

The Male Osteoporosis Risk Estimation Score (MORES) uses age, weight, and history of COPD to identify men 60 years or older who are at risk for osteoporosis (TABLE 2).¹⁸ The score can be easily calculated during a clinical encounter and is beneficial for identifying men who should be referred for DEXA scan. A score of ≥6 has been found to yield an overall sensitivity of 0.93 (95% confidence interval [CI], 0.85-0.97) and a specificity of 0.59 (95% CI, 0.56-0.62), with a number needed to screen to prevent one additional hip fracture of 279.¹⁸

The Osteoporosis Self-assessment Tool (OST) (http://depts.washington.edu/osteoed/tools.php?type=ost) is a calculated value that uses age and weight to determine an individual’s risk for osteoporosis (risk score=weight [in kg] – age [in years]/5).^16,19 Although there is not a defined value to determine a positive OST risk score, scores of -1 to 3 have been used in a variety of studies.¹⁶ In a study of 181 American men, the OST predicted osteoporosis with a sensitivity of 93% and a specificity of 66% when using a cutoff score of 3.²⁰

Treating men at risk

Pharmacologic therapy is recommended for men at an increased risk for fracture. This includes men who have had a hip or vertebral fracture without major trauma, as well as those who have not had such a fracture but have a BMD of the spine, femoral neck, and/or total hip of ≤-2.5.^5,17 This standard also applies to the radius when used as an alternative site.

Several organizations recommend screening men ages ≥70 years and those ages 50 to 69 who have risk factors for fractures or who sustained a fracture after age 50.

The International Society for Clinical Densitometry and International Osteoporosis Foundation endorse the use of the Fracture Risk Assessment Tool (FRAX). Available at http://shef.ac.uk/FRAX/tool.aspx?country=9, FRAX is a computer-based calculator that uses risk factors and BMD of the femoral neck to estimate an individual’s 10-year fracture probability.²¹ Men who are 50 years or older, have a T-score between -1.0 and -2.5 in the spine, femoral neck, or total hip, and a 10-year risk of ≥20% of developing any fracture or ≥3% of developing a hip fracture based on FRAX, should be offered pharmacotherapy.^5,17

Bisphosphonates are first-line therapy

Although oral bisphosphonates are first-line therapy for men who meet these criteria,⁴ pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy, renal disease, or malabsorption), and cost (TABLE 3).^22,23

Alendronate once weekly has been proven to increase BMD and to reduce the risk of fracture in men.^24,25 A randomized, placebo-controlled trial of 241 men with osteoporosis found that alendronate increased BMD by 7.1% (±0.3) at the lumbar spine, 2.5% (±0.4) at the femoral neck, and 2% (±0.2) for the total body. Those in the placebo group had a 1.8% (±0.5) increase in BMD of the lumbar spine, with no significant change in femoral neck or total-body BMD—and a higher incidence of vertebral fractures (7.1% vs. 0.8% for those on alendronate; P=.02).²⁴

Risedronate once daily has also been proven to increase BMD in the lumbar spine and hip, with a reduction in vertebral fractures.²⁶ Another investigation—a 2-year, multicenter double-blind placebo-controlled study of 284 men with osteoporosis—found that risedronate given once a week increased BMD in the spine and hip, but did not reduce the incidence of either vertebral or nonvertebral fractures.²⁷

Because a DEXA scan is not always available or cost effective, a validated clinical predictive tool is preferred as an intial screening option.

Both alendronate and risedronate are effective for secondary causes of bone loss, such as corticosteroid use, androgen deprivation therapy/hypogonadism, and rheumatologic conditions.²⁸ Oral bisphosphonates may cause GI irritation, however. Abdominal pain associated with alendronate use is between 1% and 7%, vs 2% to 12% for risedronate.²³ Neither medication is recommended for use in patients with an estimated glomerular filtration rate <35 mL/min.²³ There is no clearly established duration of therapy for men.

Zoledronic acid infusions, given intravenously (IV) once a year, are available for men who cannot tolerate oral bisphosphonates. In a multicenter double-blind, placebocontrolled trial, zoledronic acid was found to reduce the risk of vertebral fractures in men with primary or hypogonadism-associated osteoporosis by 67% (1.6% vertebral fractures in the treatment group after 24 months vs 4.9% with placebo).²⁹ Given within 90 days of a hip fracture repair, zoledronic acid was associated with both a reduction in the rate of new fractures and an increased survival rate.³⁰

Adverse effects of zoledronic acid include diffuse bone pain (3%-9%), fever (9%-22%) and flu-like symptoms (1%-11%). Osteonecrosis of the jaw has been reported in <1% of patients.²³

Recombinant human parathyroid hormone stimulates bone growth

Pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy), and cost.

Teriparatide, administered subcutaneously (SC) once a day, directly stimulates bone formation. In a randomized placebo controlled trial of 437 men with a T-score of -2, teriparatide was found to increase BMD at the spine and femoral neck. Participants were randomized to receive teriparatide (20 or 40 mcg/d) or placebo. Those who received teriparatide had a doserelated increase in BMD from baseline at the spine (5.9% with 20 mcg and 9% with 40 mcg) and femoral neck (1.5% and 2.9%, respectively) compared with the placebo group.³¹ Teriparatide was shown to reduce vertebral fractures by 51% compared with placebo in a randomized study of 355 men with osteoporosis.³²

Teriparatide is indicated for men with severe osteoporosis and those for whom bisphosphonate treatment has been unsuccessful. Its use is limited to 2 years due to a dose-dependent risk of osteosarcoma. Teriparatide is contraindicated in patients with skeletal metastasis and has been associated with transient hypercalcemia 4 to 6 hours after administration.²³ Its use in combination with bisphosphonates is not recommended due to the lack of proven benefit, risk of adverse effects, and associated cost.⁵

Testosterone boosts bone density

Testosterone therapy is recommended for men with low levels of testosterone (<200 ng/dL), high risk for fracture, and contraindications to pharmacologic agents approved for the treatment of osteoporosis.⁵ Supplementation of testosterone to restore correct physiologic levels will decrease bone turnover and increase bone density.³³ In a meta-analysis of 8 trials with a total of 365 participants, testosterone administered intramuscularly was found to increase lumbar BMD by 8% compared with placebo. The effect on fractures is not known.¹²

Monoclonal antibody reduces fracture risk

Denosumab, a monoclonal antibody that prevents osteoclast formation leading to decreased bone resorption, is administered SC every 6 months.²³ In a placebo-controlled trial of 242 men with low bone mass, denosumab increased BMD at the lumbar spine (5.7%), total hip (2.4%), femoral neck (2.1%), trochanter (3.1%), and one-third radius (0.6%) compared with placebo after one year.³⁴ In men receiving androgen deprivation therapy for nonmetastatic prostate cancer, denosumab has been shown to increase BMD and reduce the incidence of vertebral fractures.³⁵

Adverse effects include hypocalcemia, hypophosphatemia, fatigue, and back pain.²³ No data exist on the ability of denosumab to reduce fracture risk in men without androgen deprivation.

Calcium and vitamin D for men at risk

Men who are at risk for or have osteoporosis should consume 1000 mg to 1200 mg of calcium per day. Ideally, this should come through dietary sources, but calcium supplementation may be added when diet is inadequate.⁵ The Institute of Medicine recommends a calcium intake of 1000 mg/d for men ages 51 to 70 years and 1200 mg/d for men ages 70 and older.³⁶

Supplementation of testosterone to restore correct physiologic levels in men with low testosterone will decrease bone turnover and increase bone density.

Men with vitamin D levels below 30 ng/mL should receive vitamin D supplementation to attain blood 25(OH) D levels of at least 30 ng/mL.⁵ The Institute of Medicine recommends a daily intake of 600 international units (IU) of vitamin D for men ages 51 to 70 and 800 IU for men 70 and older.³⁶ A recent Cochrane review on vitamin D and vitamin D analogues concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.³⁷

Counseling and follow-up

Lifestyle modification is an important means of primary prevention for osteoporosis. Advise men at risk for osteoporosis to limit alcohol consumption to 2 drinks daily.^4,5,8,10 Tell those who smoke that doing so increases their risk for osteoporotic fracture and refer them for smoking cessation counseling. Emphasize that weight-bearing exercise can improve BMD and should be done at least 3 days per week.^4,5,8,10 It is important, too, to do a medication review to look for drug-drug interactions and to discuss fall prevention strategies, such as gait training and an environmental assessment and removal of fall hazards.

A Cochrane review concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.

The evidence for monitoring treatment using BMD is not very strong.^5,14 However, the Endocrine Society recommends that response to treatment be monitored using DEXA scans every one to 2 years, with reduced frequency once the BMD has stabilized.⁵ Any patient found to have a decrease in BMD after treatment is initiated should undergo further evaluation to determine the cause of the decline.

CORRESPONDENCE
Bryan Farford, DO, Mayo Clinic Division of Regional Medicine, 742 Marsh Landing Parkway, Jacksonville Beach, FL 32250; [email protected]

With older women in the United States about 4 times more likely than their male counterparts to develop osteoporosis,^1,2 physicians often fail to screen for—or to treat—low bone mass in men. There are plenty of reasons why they should.

First and foremost: Osteoporosis is a leading cause of morbidity and mortality in the elderly.³ An estimated 8.8 million American men suffer from osteoporosis or osteopenia.³ And, although only about 20% of osteoporosis patients are male, men sustain between 30% and 40% of osteoporotic fractures.^1,2 What’s more, hip fracture in men has a mortality rate of up to 37.5%—2 to 3 times higher than that of women with hip fracture.^4,5

Clearly, then, it is crucial to be aware of the risks of osteoporosis faced by both men and women as they age. Here’s a look at what to consider, when to screen, and how to treat male patients who have, or are at risk for, osteoporosis.

Which men are at risk? 

The incidence of fractures secondary to osteoporosis varies with race/ethnicity and geography. The highest rates worldwide occur in Scandinavia and among Caucasians in the United States; black, Asian, and Hispanic populations have the lowest rates.^6,7 As with women, the risk of osteoporotic fracture in men increases with age. However, the peak incidence of fracture occurs about 10 years later in men than in women, starting at about age 70.⁸ Approximately 13% of white men older than 50 years will experience at least one osteoporotic fracture.⁹

There are 2 main types of osteoporosis: primary and secondary. Up to 40% of osteoporosis in men is primary,⁴ with bone loss due either to age (senile osteoporosis) or to an unknown cause (idiopathic osteoporosis).¹⁰ For men 70 years or older, osteoporosis is assumed to be age related. Idiopathic osteoporosis is diagnosed only in men younger than 70 who have no obvious secondary cause.¹⁰ There are numerous secondary causes, however, and most men with bone loss have at least one.⁴

Common secondary causes: Lifestyle, medical conditions, and meds

The most common causes of secondary osteoporosis in men are exposure to glucocorticoids, primary or secondary hypogonadism (low testosterone), diabetes, alcohol abuse, smoking, gastrointestinal (GI) disease, hypercalciuria, low body weight (body mass index <20 kg/m2), and immobility (TABLE 1).^4,5,8,10

Chronic use of corticosteroids, often used to treat chronic obstructive pulmonary disease (COPD), asthma, and rheumatoid arthritis, directly affects the bone, decreasing skeletal muscle, increasing immobility, and reducing intestinal absorption of calcium as well as serum testosterone levels.¹⁰ Men with androgen deficiency (which may be due to androgen deprivation therapy to treat prostate cancer) or chronic use of opioids are also at increased risk.^4,5,10-12

Diagnostic screening and criteria

The World Health Organization has established diagnostic criteria for osteoporosis using bone mineral density (BMD), reported as both T-scores and Z-scores as measured on dual-energy x-ray absorptiometry (DEXA) scan.¹³ The T-score represents the number of standard deviations above or below the mean BMD for young adults, matched for sex and race, but not age. It classifies individuals into 3 categories: normal; low (osteopenia), with a T-score between -1 and -2.5; and osteoporosis (T-score ≤-2.5).^4,14 The Z-score indicates the number of standard deviations above or below the mean for age, as well as sex and race. A Z-score of ≤-2.0 is below the expected range, indicating an increased likelihood of a secondary form of osteoporosis.¹⁴

Which men to screen?

The US Preventive Services Task Force has concluded that evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men. It therefore makes no recommendation to screen men who don't have evidence of previous fractures or secondary causes of osteoporosis.¹⁵

Other organizations agree that there is insufficient evidence to recommend routine screening for men without known osteoporotic fractures or secondary causes for osteoporosis. There are, however, some guidelines that are useful in clinical practice.

The most common causes of secondary osteoporosis in men include exposure to glucocorticoids, primary or secondary hypogonadism, diabetes, alcohol abuse, and smoking.

The Endocrine Society, American College of Physicians (ACP), and National Osteoporosis Foundation (NOF) recommend screening men ages 70 years or older, and men ages 50 to 69 who have risk factors for fracture and/or a history of fracture sustained after age 50.^5,16,17 (See “Did you know?”)^{1,2,4,5,9-12,16,17} Prior to screening, it is important to do a complete medical history and physical examination.

Screening considerations. The Endocrine Society, ACP, and NOF recommend a DEXA scan of the spine and hip for men who are at increased risk for osteoporosis and have no contraindications to drug therapy.^5,16,17 In patients who have degenerative changes of the spine and hip that would likely obscure DEXA outcomes, a scan of the radius may provide a more accurate assessment of bone status. Men receiving androgen deprivation therapy for prostate cancer will have a greater decline of bone density in the radius than in the hip or spine and are therefore ideal candidates for DEXA of the forearm, as well.^5,11 Keep in mind, however, that no studies have looked at how well, or whether, men with osteoporosis measured only in the radius respond to treatment.⁵

A DEXA scan is not always widely available, nor is it a perfect predictor of fracture risk. In addition, it is not always cost effective. For some patients, the use of a validated clinical predictive tool is preferable as an initial option.

The Male Osteoporosis Risk Estimation Score (MORES) uses age, weight, and history of COPD to identify men 60 years or older who are at risk for osteoporosis (TABLE 2).¹⁸ The score can be easily calculated during a clinical encounter and is beneficial for identifying men who should be referred for DEXA scan. A score of ≥6 has been found to yield an overall sensitivity of 0.93 (95% confidence interval [CI], 0.85-0.97) and a specificity of 0.59 (95% CI, 0.56-0.62), with a number needed to screen to prevent one additional hip fracture of 279.¹⁸

The Osteoporosis Self-assessment Tool (OST) (http://depts.washington.edu/osteoed/tools.php?type=ost) is a calculated value that uses age and weight to determine an individual’s risk for osteoporosis (risk score=weight [in kg] – age [in years]/5).^16,19 Although there is not a defined value to determine a positive OST risk score, scores of -1 to 3 have been used in a variety of studies.¹⁶ In a study of 181 American men, the OST predicted osteoporosis with a sensitivity of 93% and a specificity of 66% when using a cutoff score of 3.²⁰

Treating men at risk

Pharmacologic therapy is recommended for men at an increased risk for fracture. This includes men who have had a hip or vertebral fracture without major trauma, as well as those who have not had such a fracture but have a BMD of the spine, femoral neck, and/or total hip of ≤-2.5.^5,17 This standard also applies to the radius when used as an alternative site.

Several organizations recommend screening men ages ≥70 years and those ages 50 to 69 who have risk factors for fractures or who sustained a fracture after age 50.

The International Society for Clinical Densitometry and International Osteoporosis Foundation endorse the use of the Fracture Risk Assessment Tool (FRAX). Available at http://shef.ac.uk/FRAX/tool.aspx?country=9, FRAX is a computer-based calculator that uses risk factors and BMD of the femoral neck to estimate an individual’s 10-year fracture probability.²¹ Men who are 50 years or older, have a T-score between -1.0 and -2.5 in the spine, femoral neck, or total hip, and a 10-year risk of ≥20% of developing any fracture or ≥3% of developing a hip fracture based on FRAX, should be offered pharmacotherapy.^5,17

Bisphosphonates are first-line therapy

Although oral bisphosphonates are first-line therapy for men who meet these criteria,⁴ pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy, renal disease, or malabsorption), and cost (TABLE 3).^22,23

Alendronate once weekly has been proven to increase BMD and to reduce the risk of fracture in men.^24,25 A randomized, placebo-controlled trial of 241 men with osteoporosis found that alendronate increased BMD by 7.1% (±0.3) at the lumbar spine, 2.5% (±0.4) at the femoral neck, and 2% (±0.2) for the total body. Those in the placebo group had a 1.8% (±0.5) increase in BMD of the lumbar spine, with no significant change in femoral neck or total-body BMD—and a higher incidence of vertebral fractures (7.1% vs. 0.8% for those on alendronate; P=.02).²⁴

Risedronate once daily has also been proven to increase BMD in the lumbar spine and hip, with a reduction in vertebral fractures.²⁶ Another investigation—a 2-year, multicenter double-blind placebo-controlled study of 284 men with osteoporosis—found that risedronate given once a week increased BMD in the spine and hip, but did not reduce the incidence of either vertebral or nonvertebral fractures.²⁷

Because a DEXA scan is not always available or cost effective, a validated clinical predictive tool is preferred as an intial screening option.

Both alendronate and risedronate are effective for secondary causes of bone loss, such as corticosteroid use, androgen deprivation therapy/hypogonadism, and rheumatologic conditions.²⁸ Oral bisphosphonates may cause GI irritation, however. Abdominal pain associated with alendronate use is between 1% and 7%, vs 2% to 12% for risedronate.²³ Neither medication is recommended for use in patients with an estimated glomerular filtration rate <35 mL/min.²³ There is no clearly established duration of therapy for men.

Zoledronic acid infusions, given intravenously (IV) once a year, are available for men who cannot tolerate oral bisphosphonates. In a multicenter double-blind, placebocontrolled trial, zoledronic acid was found to reduce the risk of vertebral fractures in men with primary or hypogonadism-associated osteoporosis by 67% (1.6% vertebral fractures in the treatment group after 24 months vs 4.9% with placebo).²⁹ Given within 90 days of a hip fracture repair, zoledronic acid was associated with both a reduction in the rate of new fractures and an increased survival rate.³⁰

Adverse effects of zoledronic acid include diffuse bone pain (3%-9%), fever (9%-22%) and flu-like symptoms (1%-11%). Osteonecrosis of the jaw has been reported in <1% of patients.²³

Recombinant human parathyroid hormone stimulates bone growth

Pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy), and cost.

Teriparatide, administered subcutaneously (SC) once a day, directly stimulates bone formation. In a randomized placebo controlled trial of 437 men with a T-score of -2, teriparatide was found to increase BMD at the spine and femoral neck. Participants were randomized to receive teriparatide (20 or 40 mcg/d) or placebo. Those who received teriparatide had a doserelated increase in BMD from baseline at the spine (5.9% with 20 mcg and 9% with 40 mcg) and femoral neck (1.5% and 2.9%, respectively) compared with the placebo group.³¹ Teriparatide was shown to reduce vertebral fractures by 51% compared with placebo in a randomized study of 355 men with osteoporosis.³²

Teriparatide is indicated for men with severe osteoporosis and those for whom bisphosphonate treatment has been unsuccessful. Its use is limited to 2 years due to a dose-dependent risk of osteosarcoma. Teriparatide is contraindicated in patients with skeletal metastasis and has been associated with transient hypercalcemia 4 to 6 hours after administration.²³ Its use in combination with bisphosphonates is not recommended due to the lack of proven benefit, risk of adverse effects, and associated cost.⁵

Testosterone boosts bone density

Testosterone therapy is recommended for men with low levels of testosterone (<200 ng/dL), high risk for fracture, and contraindications to pharmacologic agents approved for the treatment of osteoporosis.⁵ Supplementation of testosterone to restore correct physiologic levels will decrease bone turnover and increase bone density.³³ In a meta-analysis of 8 trials with a total of 365 participants, testosterone administered intramuscularly was found to increase lumbar BMD by 8% compared with placebo. The effect on fractures is not known.¹²

Monoclonal antibody reduces fracture risk

Denosumab, a monoclonal antibody that prevents osteoclast formation leading to decreased bone resorption, is administered SC every 6 months.²³ In a placebo-controlled trial of 242 men with low bone mass, denosumab increased BMD at the lumbar spine (5.7%), total hip (2.4%), femoral neck (2.1%), trochanter (3.1%), and one-third radius (0.6%) compared with placebo after one year.³⁴ In men receiving androgen deprivation therapy for nonmetastatic prostate cancer, denosumab has been shown to increase BMD and reduce the incidence of vertebral fractures.³⁵

Adverse effects include hypocalcemia, hypophosphatemia, fatigue, and back pain.²³ No data exist on the ability of denosumab to reduce fracture risk in men without androgen deprivation.

Calcium and vitamin D for men at risk

Men who are at risk for or have osteoporosis should consume 1000 mg to 1200 mg of calcium per day. Ideally, this should come through dietary sources, but calcium supplementation may be added when diet is inadequate.⁵ The Institute of Medicine recommends a calcium intake of 1000 mg/d for men ages 51 to 70 years and 1200 mg/d for men ages 70 and older.³⁶

Supplementation of testosterone to restore correct physiologic levels in men with low testosterone will decrease bone turnover and increase bone density.

Men with vitamin D levels below 30 ng/mL should receive vitamin D supplementation to attain blood 25(OH) D levels of at least 30 ng/mL.⁵ The Institute of Medicine recommends a daily intake of 600 international units (IU) of vitamin D for men ages 51 to 70 and 800 IU for men 70 and older.³⁶ A recent Cochrane review on vitamin D and vitamin D analogues concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.³⁷

Counseling and follow-up

Lifestyle modification is an important means of primary prevention for osteoporosis. Advise men at risk for osteoporosis to limit alcohol consumption to 2 drinks daily.^4,5,8,10 Tell those who smoke that doing so increases their risk for osteoporotic fracture and refer them for smoking cessation counseling. Emphasize that weight-bearing exercise can improve BMD and should be done at least 3 days per week.^4,5,8,10 It is important, too, to do a medication review to look for drug-drug interactions and to discuss fall prevention strategies, such as gait training and an environmental assessment and removal of fall hazards.

A Cochrane review concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.

The evidence for monitoring treatment using BMD is not very strong.^5,14 However, the Endocrine Society recommends that response to treatment be monitored using DEXA scans every one to 2 years, with reduced frequency once the BMD has stabilized.⁵ Any patient found to have a decrease in BMD after treatment is initiated should undergo further evaluation to determine the cause of the decline.

CORRESPONDENCE
Bryan Farford, DO, Mayo Clinic Division of Regional Medicine, 742 Marsh Landing Parkway, Jacksonville Beach, FL 32250; [email protected]

With older women in the United States about 4 times more likely than their male counterparts to develop osteoporosis,^1,2 physicians often fail to screen for—or to treat—low bone mass in men. There are plenty of reasons why they should.

First and foremost: Osteoporosis is a leading cause of morbidity and mortality in the elderly.³ An estimated 8.8 million American men suffer from osteoporosis or osteopenia.³ And, although only about 20% of osteoporosis patients are male, men sustain between 30% and 40% of osteoporotic fractures.^1,2 What’s more, hip fracture in men has a mortality rate of up to 37.5%—2 to 3 times higher than that of women with hip fracture.^4,5

Clearly, then, it is crucial to be aware of the risks of osteoporosis faced by both men and women as they age. Here’s a look at what to consider, when to screen, and how to treat male patients who have, or are at risk for, osteoporosis.

Which men are at risk? 

The incidence of fractures secondary to osteoporosis varies with race/ethnicity and geography. The highest rates worldwide occur in Scandinavia and among Caucasians in the United States; black, Asian, and Hispanic populations have the lowest rates.^6,7 As with women, the risk of osteoporotic fracture in men increases with age. However, the peak incidence of fracture occurs about 10 years later in men than in women, starting at about age 70.⁸ Approximately 13% of white men older than 50 years will experience at least one osteoporotic fracture.⁹

There are 2 main types of osteoporosis: primary and secondary. Up to 40% of osteoporosis in men is primary,⁴ with bone loss due either to age (senile osteoporosis) or to an unknown cause (idiopathic osteoporosis).¹⁰ For men 70 years or older, osteoporosis is assumed to be age related. Idiopathic osteoporosis is diagnosed only in men younger than 70 who have no obvious secondary cause.¹⁰ There are numerous secondary causes, however, and most men with bone loss have at least one.⁴

Common secondary causes: Lifestyle, medical conditions, and meds

The most common causes of secondary osteoporosis in men are exposure to glucocorticoids, primary or secondary hypogonadism (low testosterone), diabetes, alcohol abuse, smoking, gastrointestinal (GI) disease, hypercalciuria, low body weight (body mass index <20 kg/m2), and immobility (TABLE 1).^4,5,8,10

Chronic use of corticosteroids, often used to treat chronic obstructive pulmonary disease (COPD), asthma, and rheumatoid arthritis, directly affects the bone, decreasing skeletal muscle, increasing immobility, and reducing intestinal absorption of calcium as well as serum testosterone levels.¹⁰ Men with androgen deficiency (which may be due to androgen deprivation therapy to treat prostate cancer) or chronic use of opioids are also at increased risk.^4,5,10-12

Diagnostic screening and criteria

The World Health Organization has established diagnostic criteria for osteoporosis using bone mineral density (BMD), reported as both T-scores and Z-scores as measured on dual-energy x-ray absorptiometry (DEXA) scan.¹³ The T-score represents the number of standard deviations above or below the mean BMD for young adults, matched for sex and race, but not age. It classifies individuals into 3 categories: normal; low (osteopenia), with a T-score between -1 and -2.5; and osteoporosis (T-score ≤-2.5).^4,14 The Z-score indicates the number of standard deviations above or below the mean for age, as well as sex and race. A Z-score of ≤-2.0 is below the expected range, indicating an increased likelihood of a secondary form of osteoporosis.¹⁴

Which men to screen?

The US Preventive Services Task Force has concluded that evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men. It therefore makes no recommendation to screen men who don't have evidence of previous fractures or secondary causes of osteoporosis.¹⁵

Other organizations agree that there is insufficient evidence to recommend routine screening for men without known osteoporotic fractures or secondary causes for osteoporosis. There are, however, some guidelines that are useful in clinical practice.

The most common causes of secondary osteoporosis in men include exposure to glucocorticoids, primary or secondary hypogonadism, diabetes, alcohol abuse, and smoking.

The Endocrine Society, American College of Physicians (ACP), and National Osteoporosis Foundation (NOF) recommend screening men ages 70 years or older, and men ages 50 to 69 who have risk factors for fracture and/or a history of fracture sustained after age 50.^5,16,17 (See “Did you know?”)^{1,2,4,5,9-12,16,17} Prior to screening, it is important to do a complete medical history and physical examination.

Screening considerations. The Endocrine Society, ACP, and NOF recommend a DEXA scan of the spine and hip for men who are at increased risk for osteoporosis and have no contraindications to drug therapy.^5,16,17 In patients who have degenerative changes of the spine and hip that would likely obscure DEXA outcomes, a scan of the radius may provide a more accurate assessment of bone status. Men receiving androgen deprivation therapy for prostate cancer will have a greater decline of bone density in the radius than in the hip or spine and are therefore ideal candidates for DEXA of the forearm, as well.^5,11 Keep in mind, however, that no studies have looked at how well, or whether, men with osteoporosis measured only in the radius respond to treatment.⁵

A DEXA scan is not always widely available, nor is it a perfect predictor of fracture risk. In addition, it is not always cost effective. For some patients, the use of a validated clinical predictive tool is preferable as an initial option.

The Male Osteoporosis Risk Estimation Score (MORES) uses age, weight, and history of COPD to identify men 60 years or older who are at risk for osteoporosis (TABLE 2).¹⁸ The score can be easily calculated during a clinical encounter and is beneficial for identifying men who should be referred for DEXA scan. A score of ≥6 has been found to yield an overall sensitivity of 0.93 (95% confidence interval [CI], 0.85-0.97) and a specificity of 0.59 (95% CI, 0.56-0.62), with a number needed to screen to prevent one additional hip fracture of 279.¹⁸

The Osteoporosis Self-assessment Tool (OST) (http://depts.washington.edu/osteoed/tools.php?type=ost) is a calculated value that uses age and weight to determine an individual’s risk for osteoporosis (risk score=weight [in kg] – age [in years]/5).^16,19 Although there is not a defined value to determine a positive OST risk score, scores of -1 to 3 have been used in a variety of studies.¹⁶ In a study of 181 American men, the OST predicted osteoporosis with a sensitivity of 93% and a specificity of 66% when using a cutoff score of 3.²⁰

Treating men at risk

Pharmacologic therapy is recommended for men at an increased risk for fracture. This includes men who have had a hip or vertebral fracture without major trauma, as well as those who have not had such a fracture but have a BMD of the spine, femoral neck, and/or total hip of ≤-2.5.^5,17 This standard also applies to the radius when used as an alternative site.

Several organizations recommend screening men ages ≥70 years and those ages 50 to 69 who have risk factors for fractures or who sustained a fracture after age 50.

The International Society for Clinical Densitometry and International Osteoporosis Foundation endorse the use of the Fracture Risk Assessment Tool (FRAX). Available at http://shef.ac.uk/FRAX/tool.aspx?country=9, FRAX is a computer-based calculator that uses risk factors and BMD of the femoral neck to estimate an individual’s 10-year fracture probability.²¹ Men who are 50 years or older, have a T-score between -1.0 and -2.5 in the spine, femoral neck, or total hip, and a 10-year risk of ≥20% of developing any fracture or ≥3% of developing a hip fracture based on FRAX, should be offered pharmacotherapy.^5,17

Bisphosphonates are first-line therapy

Although oral bisphosphonates are first-line therapy for men who meet these criteria,⁴ pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy, renal disease, or malabsorption), and cost (TABLE 3).^22,23

Alendronate once weekly has been proven to increase BMD and to reduce the risk of fracture in men.^24,25 A randomized, placebo-controlled trial of 241 men with osteoporosis found that alendronate increased BMD by 7.1% (±0.3) at the lumbar spine, 2.5% (±0.4) at the femoral neck, and 2% (±0.2) for the total body. Those in the placebo group had a 1.8% (±0.5) increase in BMD of the lumbar spine, with no significant change in femoral neck or total-body BMD—and a higher incidence of vertebral fractures (7.1% vs. 0.8% for those on alendronate; P=.02).²⁴

Risedronate once daily has also been proven to increase BMD in the lumbar spine and hip, with a reduction in vertebral fractures.²⁶ Another investigation—a 2-year, multicenter double-blind placebo-controlled study of 284 men with osteoporosis—found that risedronate given once a week increased BMD in the spine and hip, but did not reduce the incidence of either vertebral or nonvertebral fractures.²⁷

Because a DEXA scan is not always available or cost effective, a validated clinical predictive tool is preferred as an intial screening option.

Both alendronate and risedronate are effective for secondary causes of bone loss, such as corticosteroid use, androgen deprivation therapy/hypogonadism, and rheumatologic conditions.²⁸ Oral bisphosphonates may cause GI irritation, however. Abdominal pain associated with alendronate use is between 1% and 7%, vs 2% to 12% for risedronate.²³ Neither medication is recommended for use in patients with an estimated glomerular filtration rate <35 mL/min.²³ There is no clearly established duration of therapy for men.

Zoledronic acid infusions, given intravenously (IV) once a year, are available for men who cannot tolerate oral bisphosphonates. In a multicenter double-blind, placebocontrolled trial, zoledronic acid was found to reduce the risk of vertebral fractures in men with primary or hypogonadism-associated osteoporosis by 67% (1.6% vertebral fractures in the treatment group after 24 months vs 4.9% with placebo).²⁹ Given within 90 days of a hip fracture repair, zoledronic acid was associated with both a reduction in the rate of new fractures and an increased survival rate.³⁰

Adverse effects of zoledronic acid include diffuse bone pain (3%-9%), fever (9%-22%) and flu-like symptoms (1%-11%). Osteonecrosis of the jaw has been reported in <1% of patients.²³

Recombinant human parathyroid hormone stimulates bone growth

Pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy), and cost.

Teriparatide, administered subcutaneously (SC) once a day, directly stimulates bone formation. In a randomized placebo controlled trial of 437 men with a T-score of -2, teriparatide was found to increase BMD at the spine and femoral neck. Participants were randomized to receive teriparatide (20 or 40 mcg/d) or placebo. Those who received teriparatide had a doserelated increase in BMD from baseline at the spine (5.9% with 20 mcg and 9% with 40 mcg) and femoral neck (1.5% and 2.9%, respectively) compared with the placebo group.³¹ Teriparatide was shown to reduce vertebral fractures by 51% compared with placebo in a randomized study of 355 men with osteoporosis.³²

Teriparatide is indicated for men with severe osteoporosis and those for whom bisphosphonate treatment has been unsuccessful. Its use is limited to 2 years due to a dose-dependent risk of osteosarcoma. Teriparatide is contraindicated in patients with skeletal metastasis and has been associated with transient hypercalcemia 4 to 6 hours after administration.²³ Its use in combination with bisphosphonates is not recommended due to the lack of proven benefit, risk of adverse effects, and associated cost.⁵

Testosterone boosts bone density

Testosterone therapy is recommended for men with low levels of testosterone (<200 ng/dL), high risk for fracture, and contraindications to pharmacologic agents approved for the treatment of osteoporosis.⁵ Supplementation of testosterone to restore correct physiologic levels will decrease bone turnover and increase bone density.³³ In a meta-analysis of 8 trials with a total of 365 participants, testosterone administered intramuscularly was found to increase lumbar BMD by 8% compared with placebo. The effect on fractures is not known.¹²

Monoclonal antibody reduces fracture risk

Denosumab, a monoclonal antibody that prevents osteoclast formation leading to decreased bone resorption, is administered SC every 6 months.²³ In a placebo-controlled trial of 242 men with low bone mass, denosumab increased BMD at the lumbar spine (5.7%), total hip (2.4%), femoral neck (2.1%), trochanter (3.1%), and one-third radius (0.6%) compared with placebo after one year.³⁴ In men receiving androgen deprivation therapy for nonmetastatic prostate cancer, denosumab has been shown to increase BMD and reduce the incidence of vertebral fractures.³⁵

Adverse effects include hypocalcemia, hypophosphatemia, fatigue, and back pain.²³ No data exist on the ability of denosumab to reduce fracture risk in men without androgen deprivation.

Calcium and vitamin D for men at risk

Men who are at risk for or have osteoporosis should consume 1000 mg to 1200 mg of calcium per day. Ideally, this should come through dietary sources, but calcium supplementation may be added when diet is inadequate.⁵ The Institute of Medicine recommends a calcium intake of 1000 mg/d for men ages 51 to 70 years and 1200 mg/d for men ages 70 and older.³⁶

Supplementation of testosterone to restore correct physiologic levels in men with low testosterone will decrease bone turnover and increase bone density.

Men with vitamin D levels below 30 ng/mL should receive vitamin D supplementation to attain blood 25(OH) D levels of at least 30 ng/mL.⁵ The Institute of Medicine recommends a daily intake of 600 international units (IU) of vitamin D for men ages 51 to 70 and 800 IU for men 70 and older.³⁶ A recent Cochrane review on vitamin D and vitamin D analogues concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.³⁷

Counseling and follow-up

Lifestyle modification is an important means of primary prevention for osteoporosis. Advise men at risk for osteoporosis to limit alcohol consumption to 2 drinks daily.^4,5,8,10 Tell those who smoke that doing so increases their risk for osteoporotic fracture and refer them for smoking cessation counseling. Emphasize that weight-bearing exercise can improve BMD and should be done at least 3 days per week.^4,5,8,10 It is important, too, to do a medication review to look for drug-drug interactions and to discuss fall prevention strategies, such as gait training and an environmental assessment and removal of fall hazards.

A Cochrane review concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.

The evidence for monitoring treatment using BMD is not very strong.^5,14 However, the Endocrine Society recommends that response to treatment be monitored using DEXA scans every one to 2 years, with reduced frequency once the BMD has stabilized.⁵ Any patient found to have a decrease in BMD after treatment is initiated should undergo further evaluation to determine the cause of the decline.

CORRESPONDENCE
Bryan Farford, DO, Mayo Clinic Division of Regional Medicine, 742 Marsh Landing Parkway, Jacksonville Beach, FL 32250; [email protected]

With older women in the United States about 4 times more likely than their male counterparts to develop osteoporosis,^1,2 physicians often fail to screen for—or to treat—low bone mass in men. There are plenty of reasons why they should.

First and foremost: Osteoporosis is a leading cause of morbidity and mortality in the elderly.³ An estimated 8.8 million American men suffer from osteoporosis or osteopenia.³ And, although only about 20% of osteoporosis patients are male, men sustain between 30% and 40% of osteoporotic fractures.^1,2 What’s more, hip fracture in men has a mortality rate of up to 37.5%—2 to 3 times higher than that of women with hip fracture.^4,5

Clearly, then, it is crucial to be aware of the risks of osteoporosis faced by both men and women as they age. Here’s a look at what to consider, when to screen, and how to treat male patients who have, or are at risk for, osteoporosis.

Which men are at risk? 

The incidence of fractures secondary to osteoporosis varies with race/ethnicity and geography. The highest rates worldwide occur in Scandinavia and among Caucasians in the United States; black, Asian, and Hispanic populations have the lowest rates.^6,7 As with women, the risk of osteoporotic fracture in men increases with age. However, the peak incidence of fracture occurs about 10 years later in men than in women, starting at about age 70.⁸ Approximately 13% of white men older than 50 years will experience at least one osteoporotic fracture.⁹

There are 2 main types of osteoporosis: primary and secondary. Up to 40% of osteoporosis in men is primary,⁴ with bone loss due either to age (senile osteoporosis) or to an unknown cause (idiopathic osteoporosis).¹⁰ For men 70 years or older, osteoporosis is assumed to be age related. Idiopathic osteoporosis is diagnosed only in men younger than 70 who have no obvious secondary cause.¹⁰ There are numerous secondary causes, however, and most men with bone loss have at least one.⁴

Common secondary causes: Lifestyle, medical conditions, and meds

The most common causes of secondary osteoporosis in men are exposure to glucocorticoids, primary or secondary hypogonadism (low testosterone), diabetes, alcohol abuse, smoking, gastrointestinal (GI) disease, hypercalciuria, low body weight (body mass index <20 kg/m2), and immobility (TABLE 1).^4,5,8,10

Chronic use of corticosteroids, often used to treat chronic obstructive pulmonary disease (COPD), asthma, and rheumatoid arthritis, directly affects the bone, decreasing skeletal muscle, increasing immobility, and reducing intestinal absorption of calcium as well as serum testosterone levels.¹⁰ Men with androgen deficiency (which may be due to androgen deprivation therapy to treat prostate cancer) or chronic use of opioids are also at increased risk.^4,5,10-12

Diagnostic screening and criteria

The World Health Organization has established diagnostic criteria for osteoporosis using bone mineral density (BMD), reported as both T-scores and Z-scores as measured on dual-energy x-ray absorptiometry (DEXA) scan.¹³ The T-score represents the number of standard deviations above or below the mean BMD for young adults, matched for sex and race, but not age. It classifies individuals into 3 categories: normal; low (osteopenia), with a T-score between -1 and -2.5; and osteoporosis (T-score ≤-2.5).^4,14 The Z-score indicates the number of standard deviations above or below the mean for age, as well as sex and race. A Z-score of ≤-2.0 is below the expected range, indicating an increased likelihood of a secondary form of osteoporosis.¹⁴

Which men to screen?

The US Preventive Services Task Force has concluded that evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men. It therefore makes no recommendation to screen men who don't have evidence of previous fractures or secondary causes of osteoporosis.¹⁵

Other organizations agree that there is insufficient evidence to recommend routine screening for men without known osteoporotic fractures or secondary causes for osteoporosis. There are, however, some guidelines that are useful in clinical practice.

The most common causes of secondary osteoporosis in men include exposure to glucocorticoids, primary or secondary hypogonadism, diabetes, alcohol abuse, and smoking.

The Endocrine Society, American College of Physicians (ACP), and National Osteoporosis Foundation (NOF) recommend screening men ages 70 years or older, and men ages 50 to 69 who have risk factors for fracture and/or a history of fracture sustained after age 50.^5,16,17 (See “Did you know?”)^{1,2,4,5,9-12,16,17} Prior to screening, it is important to do a complete medical history and physical examination.

Screening considerations. The Endocrine Society, ACP, and NOF recommend a DEXA scan of the spine and hip for men who are at increased risk for osteoporosis and have no contraindications to drug therapy.^5,16,17 In patients who have degenerative changes of the spine and hip that would likely obscure DEXA outcomes, a scan of the radius may provide a more accurate assessment of bone status. Men receiving androgen deprivation therapy for prostate cancer will have a greater decline of bone density in the radius than in the hip or spine and are therefore ideal candidates for DEXA of the forearm, as well.^5,11 Keep in mind, however, that no studies have looked at how well, or whether, men with osteoporosis measured only in the radius respond to treatment.⁵

A DEXA scan is not always widely available, nor is it a perfect predictor of fracture risk. In addition, it is not always cost effective. For some patients, the use of a validated clinical predictive tool is preferable as an initial option.

The Male Osteoporosis Risk Estimation Score (MORES) uses age, weight, and history of COPD to identify men 60 years or older who are at risk for osteoporosis (TABLE 2).¹⁸ The score can be easily calculated during a clinical encounter and is beneficial for identifying men who should be referred for DEXA scan. A score of ≥6 has been found to yield an overall sensitivity of 0.93 (95% confidence interval [CI], 0.85-0.97) and a specificity of 0.59 (95% CI, 0.56-0.62), with a number needed to screen to prevent one additional hip fracture of 279.¹⁸

The Osteoporosis Self-assessment Tool (OST) (http://depts.washington.edu/osteoed/tools.php?type=ost) is a calculated value that uses age and weight to determine an individual’s risk for osteoporosis (risk score=weight [in kg] – age [in years]/5).^16,19 Although there is not a defined value to determine a positive OST risk score, scores of -1 to 3 have been used in a variety of studies.¹⁶ In a study of 181 American men, the OST predicted osteoporosis with a sensitivity of 93% and a specificity of 66% when using a cutoff score of 3.²⁰

Treating men at risk

Pharmacologic therapy is recommended for men at an increased risk for fracture. This includes men who have had a hip or vertebral fracture without major trauma, as well as those who have not had such a fracture but have a BMD of the spine, femoral neck, and/or total hip of ≤-2.5.^5,17 This standard also applies to the radius when used as an alternative site.

Several organizations recommend screening men ages ≥70 years and those ages 50 to 69 who have risk factors for fractures or who sustained a fracture after age 50.

The International Society for Clinical Densitometry and International Osteoporosis Foundation endorse the use of the Fracture Risk Assessment Tool (FRAX). Available at http://shef.ac.uk/FRAX/tool.aspx?country=9, FRAX is a computer-based calculator that uses risk factors and BMD of the femoral neck to estimate an individual’s 10-year fracture probability.²¹ Men who are 50 years or older, have a T-score between -1.0 and -2.5 in the spine, femoral neck, or total hip, and a 10-year risk of ≥20% of developing any fracture or ≥3% of developing a hip fracture based on FRAX, should be offered pharmacotherapy.^5,17

Bisphosphonates are first-line therapy

Although oral bisphosphonates are first-line therapy for men who meet these criteria,⁴ pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy, renal disease, or malabsorption), and cost (TABLE 3).^22,23

Alendronate once weekly has been proven to increase BMD and to reduce the risk of fracture in men.^24,25 A randomized, placebo-controlled trial of 241 men with osteoporosis found that alendronate increased BMD by 7.1% (±0.3) at the lumbar spine, 2.5% (±0.4) at the femoral neck, and 2% (±0.2) for the total body. Those in the placebo group had a 1.8% (±0.5) increase in BMD of the lumbar spine, with no significant change in femoral neck or total-body BMD—and a higher incidence of vertebral fractures (7.1% vs. 0.8% for those on alendronate; P=.02).²⁴

Risedronate once daily has also been proven to increase BMD in the lumbar spine and hip, with a reduction in vertebral fractures.²⁶ Another investigation—a 2-year, multicenter double-blind placebo-controlled study of 284 men with osteoporosis—found that risedronate given once a week increased BMD in the spine and hip, but did not reduce the incidence of either vertebral or nonvertebral fractures.²⁷

Because a DEXA scan is not always available or cost effective, a validated clinical predictive tool is preferred as an intial screening option.

Both alendronate and risedronate are effective for secondary causes of bone loss, such as corticosteroid use, androgen deprivation therapy/hypogonadism, and rheumatologic conditions.²⁸ Oral bisphosphonates may cause GI irritation, however. Abdominal pain associated with alendronate use is between 1% and 7%, vs 2% to 12% for risedronate.²³ Neither medication is recommended for use in patients with an estimated glomerular filtration rate <35 mL/min.²³ There is no clearly established duration of therapy for men.

Zoledronic acid infusions, given intravenously (IV) once a year, are available for men who cannot tolerate oral bisphosphonates. In a multicenter double-blind, placebocontrolled trial, zoledronic acid was found to reduce the risk of vertebral fractures in men with primary or hypogonadism-associated osteoporosis by 67% (1.6% vertebral fractures in the treatment group after 24 months vs 4.9% with placebo).²⁹ Given within 90 days of a hip fracture repair, zoledronic acid was associated with both a reduction in the rate of new fractures and an increased survival rate.³⁰

Adverse effects of zoledronic acid include diffuse bone pain (3%-9%), fever (9%-22%) and flu-like symptoms (1%-11%). Osteonecrosis of the jaw has been reported in <1% of patients.²³

Recombinant human parathyroid hormone stimulates bone growth

Pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy), and cost.

Teriparatide, administered subcutaneously (SC) once a day, directly stimulates bone formation. In a randomized placebo controlled trial of 437 men with a T-score of -2, teriparatide was found to increase BMD at the spine and femoral neck. Participants were randomized to receive teriparatide (20 or 40 mcg/d) or placebo. Those who received teriparatide had a doserelated increase in BMD from baseline at the spine (5.9% with 20 mcg and 9% with 40 mcg) and femoral neck (1.5% and 2.9%, respectively) compared with the placebo group.³¹ Teriparatide was shown to reduce vertebral fractures by 51% compared with placebo in a randomized study of 355 men with osteoporosis.³²

Teriparatide is indicated for men with severe osteoporosis and those for whom bisphosphonate treatment has been unsuccessful. Its use is limited to 2 years due to a dose-dependent risk of osteosarcoma. Teriparatide is contraindicated in patients with skeletal metastasis and has been associated with transient hypercalcemia 4 to 6 hours after administration.²³ Its use in combination with bisphosphonates is not recommended due to the lack of proven benefit, risk of adverse effects, and associated cost.⁵

Testosterone boosts bone density

Testosterone therapy is recommended for men with low levels of testosterone (<200 ng/dL), high risk for fracture, and contraindications to pharmacologic agents approved for the treatment of osteoporosis.⁵ Supplementation of testosterone to restore correct physiologic levels will decrease bone turnover and increase bone density.³³ In a meta-analysis of 8 trials with a total of 365 participants, testosterone administered intramuscularly was found to increase lumbar BMD by 8% compared with placebo. The effect on fractures is not known.¹²

Monoclonal antibody reduces fracture risk

Denosumab, a monoclonal antibody that prevents osteoclast formation leading to decreased bone resorption, is administered SC every 6 months.²³ In a placebo-controlled trial of 242 men with low bone mass, denosumab increased BMD at the lumbar spine (5.7%), total hip (2.4%), femoral neck (2.1%), trochanter (3.1%), and one-third radius (0.6%) compared with placebo after one year.³⁴ In men receiving androgen deprivation therapy for nonmetastatic prostate cancer, denosumab has been shown to increase BMD and reduce the incidence of vertebral fractures.³⁵

Adverse effects include hypocalcemia, hypophosphatemia, fatigue, and back pain.²³ No data exist on the ability of denosumab to reduce fracture risk in men without androgen deprivation.

Calcium and vitamin D for men at risk

Men who are at risk for or have osteoporosis should consume 1000 mg to 1200 mg of calcium per day. Ideally, this should come through dietary sources, but calcium supplementation may be added when diet is inadequate.⁵ The Institute of Medicine recommends a calcium intake of 1000 mg/d for men ages 51 to 70 years and 1200 mg/d for men ages 70 and older.³⁶

Supplementation of testosterone to restore correct physiologic levels in men with low testosterone will decrease bone turnover and increase bone density.

Men with vitamin D levels below 30 ng/mL should receive vitamin D supplementation to attain blood 25(OH) D levels of at least 30 ng/mL.⁵ The Institute of Medicine recommends a daily intake of 600 international units (IU) of vitamin D for men ages 51 to 70 and 800 IU for men 70 and older.³⁶ A recent Cochrane review on vitamin D and vitamin D analogues concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.³⁷

Counseling and follow-up

Lifestyle modification is an important means of primary prevention for osteoporosis. Advise men at risk for osteoporosis to limit alcohol consumption to 2 drinks daily.^4,5,8,10 Tell those who smoke that doing so increases their risk for osteoporotic fracture and refer them for smoking cessation counseling. Emphasize that weight-bearing exercise can improve BMD and should be done at least 3 days per week.^4,5,8,10 It is important, too, to do a medication review to look for drug-drug interactions and to discuss fall prevention strategies, such as gait training and an environmental assessment and removal of fall hazards.

A Cochrane review concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.

The evidence for monitoring treatment using BMD is not very strong.^5,14 However, the Endocrine Society recommends that response to treatment be monitored using DEXA scans every one to 2 years, with reduced frequency once the BMD has stabilized.⁵ Any patient found to have a decrease in BMD after treatment is initiated should undergo further evaluation to determine the cause of the decline.

CORRESPONDENCE
Bryan Farford, DO, Mayo Clinic Division of Regional Medicine, 742 Marsh Landing Parkway, Jacksonville Beach, FL 32250; [email protected]

With older women in the United States about 4 times more likely than their male counterparts to develop osteoporosis,^1,2 physicians often fail to screen for—or to treat—low bone mass in men. There are plenty of reasons why they should.

First and foremost: Osteoporosis is a leading cause of morbidity and mortality in the elderly.³ An estimated 8.8 million American men suffer from osteoporosis or osteopenia.³ And, although only about 20% of osteoporosis patients are male, men sustain between 30% and 40% of osteoporotic fractures.^1,2 What’s more, hip fracture in men has a mortality rate of up to 37.5%—2 to 3 times higher than that of women with hip fracture.^4,5

Clearly, then, it is crucial to be aware of the risks of osteoporosis faced by both men and women as they age. Here’s a look at what to consider, when to screen, and how to treat male patients who have, or are at risk for, osteoporosis.

Which men are at risk? 

The incidence of fractures secondary to osteoporosis varies with race/ethnicity and geography. The highest rates worldwide occur in Scandinavia and among Caucasians in the United States; black, Asian, and Hispanic populations have the lowest rates.^6,7 As with women, the risk of osteoporotic fracture in men increases with age. However, the peak incidence of fracture occurs about 10 years later in men than in women, starting at about age 70.⁸ Approximately 13% of white men older than 50 years will experience at least one osteoporotic fracture.⁹

There are 2 main types of osteoporosis: primary and secondary. Up to 40% of osteoporosis in men is primary,⁴ with bone loss due either to age (senile osteoporosis) or to an unknown cause (idiopathic osteoporosis).¹⁰ For men 70 years or older, osteoporosis is assumed to be age related. Idiopathic osteoporosis is diagnosed only in men younger than 70 who have no obvious secondary cause.¹⁰ There are numerous secondary causes, however, and most men with bone loss have at least one.⁴

Common secondary causes: Lifestyle, medical conditions, and meds

The most common causes of secondary osteoporosis in men are exposure to glucocorticoids, primary or secondary hypogonadism (low testosterone), diabetes, alcohol abuse, smoking, gastrointestinal (GI) disease, hypercalciuria, low body weight (body mass index <20 kg/m2), and immobility (TABLE 1).^4,5,8,10

Chronic use of corticosteroids, often used to treat chronic obstructive pulmonary disease (COPD), asthma, and rheumatoid arthritis, directly affects the bone, decreasing skeletal muscle, increasing immobility, and reducing intestinal absorption of calcium as well as serum testosterone levels.¹⁰ Men with androgen deficiency (which may be due to androgen deprivation therapy to treat prostate cancer) or chronic use of opioids are also at increased risk.^4,5,10-12

Diagnostic screening and criteria

The World Health Organization has established diagnostic criteria for osteoporosis using bone mineral density (BMD), reported as both T-scores and Z-scores as measured on dual-energy x-ray absorptiometry (DEXA) scan.¹³ The T-score represents the number of standard deviations above or below the mean BMD for young adults, matched for sex and race, but not age. It classifies individuals into 3 categories: normal; low (osteopenia), with a T-score between -1 and -2.5; and osteoporosis (T-score ≤-2.5).^4,14 The Z-score indicates the number of standard deviations above or below the mean for age, as well as sex and race. A Z-score of ≤-2.0 is below the expected range, indicating an increased likelihood of a secondary form of osteoporosis.¹⁴

Which men to screen?

The US Preventive Services Task Force has concluded that evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men. It therefore makes no recommendation to screen men who don't have evidence of previous fractures or secondary causes of osteoporosis.¹⁵

Other organizations agree that there is insufficient evidence to recommend routine screening for men without known osteoporotic fractures or secondary causes for osteoporosis. There are, however, some guidelines that are useful in clinical practice.

The most common causes of secondary osteoporosis in men include exposure to glucocorticoids, primary or secondary hypogonadism, diabetes, alcohol abuse, and smoking.

The Endocrine Society, American College of Physicians (ACP), and National Osteoporosis Foundation (NOF) recommend screening men ages 70 years or older, and men ages 50 to 69 who have risk factors for fracture and/or a history of fracture sustained after age 50.^5,16,17 (See “Did you know?”)^{1,2,4,5,9-12,16,17} Prior to screening, it is important to do a complete medical history and physical examination.

Screening considerations. The Endocrine Society, ACP, and NOF recommend a DEXA scan of the spine and hip for men who are at increased risk for osteoporosis and have no contraindications to drug therapy.^5,16,17 In patients who have degenerative changes of the spine and hip that would likely obscure DEXA outcomes, a scan of the radius may provide a more accurate assessment of bone status. Men receiving androgen deprivation therapy for prostate cancer will have a greater decline of bone density in the radius than in the hip or spine and are therefore ideal candidates for DEXA of the forearm, as well.^5,11 Keep in mind, however, that no studies have looked at how well, or whether, men with osteoporosis measured only in the radius respond to treatment.⁵

A DEXA scan is not always widely available, nor is it a perfect predictor of fracture risk. In addition, it is not always cost effective. For some patients, the use of a validated clinical predictive tool is preferable as an initial option.

The Male Osteoporosis Risk Estimation Score (MORES) uses age, weight, and history of COPD to identify men 60 years or older who are at risk for osteoporosis (TABLE 2).¹⁸ The score can be easily calculated during a clinical encounter and is beneficial for identifying men who should be referred for DEXA scan. A score of ≥6 has been found to yield an overall sensitivity of 0.93 (95% confidence interval [CI], 0.85-0.97) and a specificity of 0.59 (95% CI, 0.56-0.62), with a number needed to screen to prevent one additional hip fracture of 279.¹⁸

The Osteoporosis Self-assessment Tool (OST) (http://depts.washington.edu/osteoed/tools.php?type=ost) is a calculated value that uses age and weight to determine an individual’s risk for osteoporosis (risk score=weight [in kg] – age [in years]/5).^16,19 Although there is not a defined value to determine a positive OST risk score, scores of -1 to 3 have been used in a variety of studies.¹⁶ In a study of 181 American men, the OST predicted osteoporosis with a sensitivity of 93% and a specificity of 66% when using a cutoff score of 3.²⁰

Treating men at risk

Pharmacologic therapy is recommended for men at an increased risk for fracture. This includes men who have had a hip or vertebral fracture without major trauma, as well as those who have not had such a fracture but have a BMD of the spine, femoral neck, and/or total hip of ≤-2.5.^5,17 This standard also applies to the radius when used as an alternative site.

Several organizations recommend screening men ages ≥70 years and those ages 50 to 69 who have risk factors for fractures or who sustained a fracture after age 50.

The International Society for Clinical Densitometry and International Osteoporosis Foundation endorse the use of the Fracture Risk Assessment Tool (FRAX). Available at http://shef.ac.uk/FRAX/tool.aspx?country=9, FRAX is a computer-based calculator that uses risk factors and BMD of the femoral neck to estimate an individual’s 10-year fracture probability.²¹ Men who are 50 years or older, have a T-score between -1.0 and -2.5 in the spine, femoral neck, or total hip, and a 10-year risk of ≥20% of developing any fracture or ≥3% of developing a hip fracture based on FRAX, should be offered pharmacotherapy.^5,17

Bisphosphonates are first-line therapy

Although oral bisphosphonates are first-line therapy for men who meet these criteria,⁴ pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy, renal disease, or malabsorption), and cost (TABLE 3).^22,23

Alendronate once weekly has been proven to increase BMD and to reduce the risk of fracture in men.^24,25 A randomized, placebo-controlled trial of 241 men with osteoporosis found that alendronate increased BMD by 7.1% (±0.3) at the lumbar spine, 2.5% (±0.4) at the femoral neck, and 2% (±0.2) for the total body. Those in the placebo group had a 1.8% (±0.5) increase in BMD of the lumbar spine, with no significant change in femoral neck or total-body BMD—and a higher incidence of vertebral fractures (7.1% vs. 0.8% for those on alendronate; P=.02).²⁴

Risedronate once daily has also been proven to increase BMD in the lumbar spine and hip, with a reduction in vertebral fractures.²⁶ Another investigation—a 2-year, multicenter double-blind placebo-controlled study of 284 men with osteoporosis—found that risedronate given once a week increased BMD in the spine and hip, but did not reduce the incidence of either vertebral or nonvertebral fractures.²⁷

Because a DEXA scan is not always available or cost effective, a validated clinical predictive tool is preferred as an intial screening option.

Both alendronate and risedronate are effective for secondary causes of bone loss, such as corticosteroid use, androgen deprivation therapy/hypogonadism, and rheumatologic conditions.²⁸ Oral bisphosphonates may cause GI irritation, however. Abdominal pain associated with alendronate use is between 1% and 7%, vs 2% to 12% for risedronate.²³ Neither medication is recommended for use in patients with an estimated glomerular filtration rate <35 mL/min.²³ There is no clearly established duration of therapy for men.

Zoledronic acid infusions, given intravenously (IV) once a year, are available for men who cannot tolerate oral bisphosphonates. In a multicenter double-blind, placebocontrolled trial, zoledronic acid was found to reduce the risk of vertebral fractures in men with primary or hypogonadism-associated osteoporosis by 67% (1.6% vertebral fractures in the treatment group after 24 months vs 4.9% with placebo).²⁹ Given within 90 days of a hip fracture repair, zoledronic acid was associated with both a reduction in the rate of new fractures and an increased survival rate.³⁰

Adverse effects of zoledronic acid include diffuse bone pain (3%-9%), fever (9%-22%) and flu-like symptoms (1%-11%). Osteonecrosis of the jaw has been reported in <1% of patients.²³

Recombinant human parathyroid hormone stimulates bone growth

Pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy), and cost.

Teriparatide, administered subcutaneously (SC) once a day, directly stimulates bone formation. In a randomized placebo controlled trial of 437 men with a T-score of -2, teriparatide was found to increase BMD at the spine and femoral neck. Participants were randomized to receive teriparatide (20 or 40 mcg/d) or placebo. Those who received teriparatide had a doserelated increase in BMD from baseline at the spine (5.9% with 20 mcg and 9% with 40 mcg) and femoral neck (1.5% and 2.9%, respectively) compared with the placebo group.³¹ Teriparatide was shown to reduce vertebral fractures by 51% compared with placebo in a randomized study of 355 men with osteoporosis.³²

Teriparatide is indicated for men with severe osteoporosis and those for whom bisphosphonate treatment has been unsuccessful. Its use is limited to 2 years due to a dose-dependent risk of osteosarcoma. Teriparatide is contraindicated in patients with skeletal metastasis and has been associated with transient hypercalcemia 4 to 6 hours after administration.²³ Its use in combination with bisphosphonates is not recommended due to the lack of proven benefit, risk of adverse effects, and associated cost.⁵

Testosterone boosts bone density

Testosterone therapy is recommended for men with low levels of testosterone (<200 ng/dL), high risk for fracture, and contraindications to pharmacologic agents approved for the treatment of osteoporosis.⁵ Supplementation of testosterone to restore correct physiologic levels will decrease bone turnover and increase bone density.³³ In a meta-analysis of 8 trials with a total of 365 participants, testosterone administered intramuscularly was found to increase lumbar BMD by 8% compared with placebo. The effect on fractures is not known.¹²

Monoclonal antibody reduces fracture risk

Denosumab, a monoclonal antibody that prevents osteoclast formation leading to decreased bone resorption, is administered SC every 6 months.²³ In a placebo-controlled trial of 242 men with low bone mass, denosumab increased BMD at the lumbar spine (5.7%), total hip (2.4%), femoral neck (2.1%), trochanter (3.1%), and one-third radius (0.6%) compared with placebo after one year.³⁴ In men receiving androgen deprivation therapy for nonmetastatic prostate cancer, denosumab has been shown to increase BMD and reduce the incidence of vertebral fractures.³⁵

Adverse effects include hypocalcemia, hypophosphatemia, fatigue, and back pain.²³ No data exist on the ability of denosumab to reduce fracture risk in men without androgen deprivation.

Calcium and vitamin D for men at risk

Men who are at risk for or have osteoporosis should consume 1000 mg to 1200 mg of calcium per day. Ideally, this should come through dietary sources, but calcium supplementation may be added when diet is inadequate.⁵ The Institute of Medicine recommends a calcium intake of 1000 mg/d for men ages 51 to 70 years and 1200 mg/d for men ages 70 and older.³⁶

Supplementation of testosterone to restore correct physiologic levels in men with low testosterone will decrease bone turnover and increase bone density.

Men with vitamin D levels below 30 ng/mL should receive vitamin D supplementation to attain blood 25(OH) D levels of at least 30 ng/mL.⁵ The Institute of Medicine recommends a daily intake of 600 international units (IU) of vitamin D for men ages 51 to 70 and 800 IU for men 70 and older.³⁶ A recent Cochrane review on vitamin D and vitamin D analogues concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.³⁷

Counseling and follow-up

Lifestyle modification is an important means of primary prevention for osteoporosis. Advise men at risk for osteoporosis to limit alcohol consumption to 2 drinks daily.^4,5,8,10 Tell those who smoke that doing so increases their risk for osteoporotic fracture and refer them for smoking cessation counseling. Emphasize that weight-bearing exercise can improve BMD and should be done at least 3 days per week.^4,5,8,10 It is important, too, to do a medication review to look for drug-drug interactions and to discuss fall prevention strategies, such as gait training and an environmental assessment and removal of fall hazards.

A Cochrane review concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.

The evidence for monitoring treatment using BMD is not very strong.^5,14 However, the Endocrine Society recommends that response to treatment be monitored using DEXA scans every one to 2 years, with reduced frequency once the BMD has stabilized.⁵ Any patient found to have a decrease in BMD after treatment is initiated should undergo further evaluation to determine the cause of the decline.

CORRESPONDENCE
Bryan Farford, DO, Mayo Clinic Division of Regional Medicine, 742 Marsh Landing Parkway, Jacksonville Beach, FL 32250; [email protected]

With older women in the United States about 4 times more likely than their male counterparts to develop osteoporosis,^1,2 physicians often fail to screen for—or to treat—low bone mass in men. There are plenty of reasons why they should.

First and foremost: Osteoporosis is a leading cause of morbidity and mortality in the elderly.³ An estimated 8.8 million American men suffer from osteoporosis or osteopenia.³ And, although only about 20% of osteoporosis patients are male, men sustain between 30% and 40% of osteoporotic fractures.^1,2 What’s more, hip fracture in men has a mortality rate of up to 37.5%—2 to 3 times higher than that of women with hip fracture.^4,5

Clearly, then, it is crucial to be aware of the risks of osteoporosis faced by both men and women as they age. Here’s a look at what to consider, when to screen, and how to treat male patients who have, or are at risk for, osteoporosis.

Which men are at risk? 

The incidence of fractures secondary to osteoporosis varies with race/ethnicity and geography. The highest rates worldwide occur in Scandinavia and among Caucasians in the United States; black, Asian, and Hispanic populations have the lowest rates.^6,7 As with women, the risk of osteoporotic fracture in men increases with age. However, the peak incidence of fracture occurs about 10 years later in men than in women, starting at about age 70.⁸ Approximately 13% of white men older than 50 years will experience at least one osteoporotic fracture.⁹

There are 2 main types of osteoporosis: primary and secondary. Up to 40% of osteoporosis in men is primary,⁴ with bone loss due either to age (senile osteoporosis) or to an unknown cause (idiopathic osteoporosis).¹⁰ For men 70 years or older, osteoporosis is assumed to be age related. Idiopathic osteoporosis is diagnosed only in men younger than 70 who have no obvious secondary cause.¹⁰ There are numerous secondary causes, however, and most men with bone loss have at least one.⁴

Common secondary causes: Lifestyle, medical conditions, and meds

The most common causes of secondary osteoporosis in men are exposure to glucocorticoids, primary or secondary hypogonadism (low testosterone), diabetes, alcohol abuse, smoking, gastrointestinal (GI) disease, hypercalciuria, low body weight (body mass index <20 kg/m2), and immobility (TABLE 1).^4,5,8,10

Chronic use of corticosteroids, often used to treat chronic obstructive pulmonary disease (COPD), asthma, and rheumatoid arthritis, directly affects the bone, decreasing skeletal muscle, increasing immobility, and reducing intestinal absorption of calcium as well as serum testosterone levels.¹⁰ Men with androgen deficiency (which may be due to androgen deprivation therapy to treat prostate cancer) or chronic use of opioids are also at increased risk.^4,5,10-12

Diagnostic screening and criteria

The World Health Organization has established diagnostic criteria for osteoporosis using bone mineral density (BMD), reported as both T-scores and Z-scores as measured on dual-energy x-ray absorptiometry (DEXA) scan.¹³ The T-score represents the number of standard deviations above or below the mean BMD for young adults, matched for sex and race, but not age. It classifies individuals into 3 categories: normal; low (osteopenia), with a T-score between -1 and -2.5; and osteoporosis (T-score ≤-2.5).^4,14 The Z-score indicates the number of standard deviations above or below the mean for age, as well as sex and race. A Z-score of ≤-2.0 is below the expected range, indicating an increased likelihood of a secondary form of osteoporosis.¹⁴

Which men to screen?

The US Preventive Services Task Force has concluded that evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men. It therefore makes no recommendation to screen men who don't have evidence of previous fractures or secondary causes of osteoporosis.¹⁵

Other organizations agree that there is insufficient evidence to recommend routine screening for men without known osteoporotic fractures or secondary causes for osteoporosis. There are, however, some guidelines that are useful in clinical practice.

The most common causes of secondary osteoporosis in men include exposure to glucocorticoids, primary or secondary hypogonadism, diabetes, alcohol abuse, and smoking.

The Endocrine Society, American College of Physicians (ACP), and National Osteoporosis Foundation (NOF) recommend screening men ages 70 years or older, and men ages 50 to 69 who have risk factors for fracture and/or a history of fracture sustained after age 50.^5,16,17 (See “Did you know?”)^{1,2,4,5,9-12,16,17} Prior to screening, it is important to do a complete medical history and physical examination.

Screening considerations. The Endocrine Society, ACP, and NOF recommend a DEXA scan of the spine and hip for men who are at increased risk for osteoporosis and have no contraindications to drug therapy.^5,16,17 In patients who have degenerative changes of the spine and hip that would likely obscure DEXA outcomes, a scan of the radius may provide a more accurate assessment of bone status. Men receiving androgen deprivation therapy for prostate cancer will have a greater decline of bone density in the radius than in the hip or spine and are therefore ideal candidates for DEXA of the forearm, as well.^5,11 Keep in mind, however, that no studies have looked at how well, or whether, men with osteoporosis measured only in the radius respond to treatment.⁵

A DEXA scan is not always widely available, nor is it a perfect predictor of fracture risk. In addition, it is not always cost effective. For some patients, the use of a validated clinical predictive tool is preferable as an initial option.

The Male Osteoporosis Risk Estimation Score (MORES) uses age, weight, and history of COPD to identify men 60 years or older who are at risk for osteoporosis (TABLE 2).¹⁸ The score can be easily calculated during a clinical encounter and is beneficial for identifying men who should be referred for DEXA scan. A score of ≥6 has been found to yield an overall sensitivity of 0.93 (95% confidence interval [CI], 0.85-0.97) and a specificity of 0.59 (95% CI, 0.56-0.62), with a number needed to screen to prevent one additional hip fracture of 279.¹⁸

The Osteoporosis Self-assessment Tool (OST) (http://depts.washington.edu/osteoed/tools.php?type=ost) is a calculated value that uses age and weight to determine an individual’s risk for osteoporosis (risk score=weight [in kg] – age [in years]/5).^16,19 Although there is not a defined value to determine a positive OST risk score, scores of -1 to 3 have been used in a variety of studies.¹⁶ In a study of 181 American men, the OST predicted osteoporosis with a sensitivity of 93% and a specificity of 66% when using a cutoff score of 3.²⁰

Treating men at risk

Pharmacologic therapy is recommended for men at an increased risk for fracture. This includes men who have had a hip or vertebral fracture without major trauma, as well as those who have not had such a fracture but have a BMD of the spine, femoral neck, and/or total hip of ≤-2.5.^5,17 This standard also applies to the radius when used as an alternative site.

Several organizations recommend screening men ages ≥70 years and those ages 50 to 69 who have risk factors for fractures or who sustained a fracture after age 50.

The International Society for Clinical Densitometry and International Osteoporosis Foundation endorse the use of the Fracture Risk Assessment Tool (FRAX). Available at http://shef.ac.uk/FRAX/tool.aspx?country=9, FRAX is a computer-based calculator that uses risk factors and BMD of the femoral neck to estimate an individual’s 10-year fracture probability.²¹ Men who are 50 years or older, have a T-score between -1.0 and -2.5 in the spine, femoral neck, or total hip, and a 10-year risk of ≥20% of developing any fracture or ≥3% of developing a hip fracture based on FRAX, should be offered pharmacotherapy.^5,17

Bisphosphonates are first-line therapy

Although oral bisphosphonates are first-line therapy for men who meet these criteria,⁴ pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy, renal disease, or malabsorption), and cost (TABLE 3).^22,23

Alendronate once weekly has been proven to increase BMD and to reduce the risk of fracture in men.^24,25 A randomized, placebo-controlled trial of 241 men with osteoporosis found that alendronate increased BMD by 7.1% (±0.3) at the lumbar spine, 2.5% (±0.4) at the femoral neck, and 2% (±0.2) for the total body. Those in the placebo group had a 1.8% (±0.5) increase in BMD of the lumbar spine, with no significant change in femoral neck or total-body BMD—and a higher incidence of vertebral fractures (7.1% vs. 0.8% for those on alendronate; P=.02).²⁴

Risedronate once daily has also been proven to increase BMD in the lumbar spine and hip, with a reduction in vertebral fractures.²⁶ Another investigation—a 2-year, multicenter double-blind placebo-controlled study of 284 men with osteoporosis—found that risedronate given once a week increased BMD in the spine and hip, but did not reduce the incidence of either vertebral or nonvertebral fractures.²⁷

Because a DEXA scan is not always available or cost effective, a validated clinical predictive tool is preferred as an intial screening option.

Both alendronate and risedronate are effective for secondary causes of bone loss, such as corticosteroid use, androgen deprivation therapy/hypogonadism, and rheumatologic conditions.²⁸ Oral bisphosphonates may cause GI irritation, however. Abdominal pain associated with alendronate use is between 1% and 7%, vs 2% to 12% for risedronate.²³ Neither medication is recommended for use in patients with an estimated glomerular filtration rate <35 mL/min.²³ There is no clearly established duration of therapy for men.

Zoledronic acid infusions, given intravenously (IV) once a year, are available for men who cannot tolerate oral bisphosphonates. In a multicenter double-blind, placebocontrolled trial, zoledronic acid was found to reduce the risk of vertebral fractures in men with primary or hypogonadism-associated osteoporosis by 67% (1.6% vertebral fractures in the treatment group after 24 months vs 4.9% with placebo).²⁹ Given within 90 days of a hip fracture repair, zoledronic acid was associated with both a reduction in the rate of new fractures and an increased survival rate.³⁰

Adverse effects of zoledronic acid include diffuse bone pain (3%-9%), fever (9%-22%) and flu-like symptoms (1%-11%). Osteonecrosis of the jaw has been reported in <1% of patients.²³

Recombinant human parathyroid hormone stimulates bone growth

Pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy), and cost.

Teriparatide, administered subcutaneously (SC) once a day, directly stimulates bone formation. In a randomized placebo controlled trial of 437 men with a T-score of -2, teriparatide was found to increase BMD at the spine and femoral neck. Participants were randomized to receive teriparatide (20 or 40 mcg/d) or placebo. Those who received teriparatide had a doserelated increase in BMD from baseline at the spine (5.9% with 20 mcg and 9% with 40 mcg) and femoral neck (1.5% and 2.9%, respectively) compared with the placebo group.³¹ Teriparatide was shown to reduce vertebral fractures by 51% compared with placebo in a randomized study of 355 men with osteoporosis.³²

Teriparatide is indicated for men with severe osteoporosis and those for whom bisphosphonate treatment has been unsuccessful. Its use is limited to 2 years due to a dose-dependent risk of osteosarcoma. Teriparatide is contraindicated in patients with skeletal metastasis and has been associated with transient hypercalcemia 4 to 6 hours after administration.²³ Its use in combination with bisphosphonates is not recommended due to the lack of proven benefit, risk of adverse effects, and associated cost.⁵

Testosterone boosts bone density

Testosterone therapy is recommended for men with low levels of testosterone (<200 ng/dL), high risk for fracture, and contraindications to pharmacologic agents approved for the treatment of osteoporosis.⁵ Supplementation of testosterone to restore correct physiologic levels will decrease bone turnover and increase bone density.³³ In a meta-analysis of 8 trials with a total of 365 participants, testosterone administered intramuscularly was found to increase lumbar BMD by 8% compared with placebo. The effect on fractures is not known.¹²

Monoclonal antibody reduces fracture risk

Denosumab, a monoclonal antibody that prevents osteoclast formation leading to decreased bone resorption, is administered SC every 6 months.²³ In a placebo-controlled trial of 242 men with low bone mass, denosumab increased BMD at the lumbar spine (5.7%), total hip (2.4%), femoral neck (2.1%), trochanter (3.1%), and one-third radius (0.6%) compared with placebo after one year.³⁴ In men receiving androgen deprivation therapy for nonmetastatic prostate cancer, denosumab has been shown to increase BMD and reduce the incidence of vertebral fractures.³⁵

Adverse effects include hypocalcemia, hypophosphatemia, fatigue, and back pain.²³ No data exist on the ability of denosumab to reduce fracture risk in men without androgen deprivation.

Calcium and vitamin D for men at risk

Men who are at risk for or have osteoporosis should consume 1000 mg to 1200 mg of calcium per day. Ideally, this should come through dietary sources, but calcium supplementation may be added when diet is inadequate.⁵ The Institute of Medicine recommends a calcium intake of 1000 mg/d for men ages 51 to 70 years and 1200 mg/d for men ages 70 and older.³⁶

Supplementation of testosterone to restore correct physiologic levels in men with low testosterone will decrease bone turnover and increase bone density.

Men with vitamin D levels below 30 ng/mL should receive vitamin D supplementation to attain blood 25(OH) D levels of at least 30 ng/mL.⁵ The Institute of Medicine recommends a daily intake of 600 international units (IU) of vitamin D for men ages 51 to 70 and 800 IU for men 70 and older.³⁶ A recent Cochrane review on vitamin D and vitamin D analogues concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.³⁷

Counseling and follow-up

Lifestyle modification is an important means of primary prevention for osteoporosis. Advise men at risk for osteoporosis to limit alcohol consumption to 2 drinks daily.^4,5,8,10 Tell those who smoke that doing so increases their risk for osteoporotic fracture and refer them for smoking cessation counseling. Emphasize that weight-bearing exercise can improve BMD and should be done at least 3 days per week.^4,5,8,10 It is important, too, to do a medication review to look for drug-drug interactions and to discuss fall prevention strategies, such as gait training and an environmental assessment and removal of fall hazards.

A Cochrane review concluded that vitamin D alone was unlikely to prevent fractures in older people; when taken with calcium, however, it may have a preventive effect.

The evidence for monitoring treatment using BMD is not very strong.^5,14 However, the Endocrine Society recommends that response to treatment be monitored using DEXA scans every one to 2 years, with reduced frequency once the BMD has stabilized.⁵ Any patient found to have a decrease in BMD after treatment is initiated should undergo further evaluation to determine the cause of the decline.

CORRESPONDENCE
Bryan Farford, DO, Mayo Clinic Division of Regional Medicine, 742 Marsh Landing Parkway, Jacksonville Beach, FL 32250; [email protected]

A 3-month-old boy was diagnosed with severe respiratory syncytial virus infection at a North Carolina hospital in 2009. The infant was intubated, and a transfer to another hospital that had a pediatric ICU was ordered. The second hospital’s emergency transport service facilitated the transfer.

The ambulance was staffed by an EMT-paramedic and a transport registered nurse, both certified in Pediatric Advanced Life Support (PALS). During transport, the infant was intubated and medically paralyzed with vecuronium. About 10 minutes prior to arrival, the infant’s condition worsened, and he experienced cardiac arrest. Chest compressions and heart medications were provided.

Upon arrival at the second hospital, the infant was resuscitated. An emergency department physician, Dr S., ordered reintubation, and the infant again experienced cardiac arrest. For the next 10 minutes, Dr S. ordered chest compressions and heart medication; he eventually reintubated the infant, at which point cardiac arrest ceased with a spontaneous heartbeat.

After transfer to the pediatric ICU, the infant was diagnosed with permanent hypoxic ischemic brain injury caused by the cardiac episodes and low oxygen intake. At the time of trial, the child could not walk, talk, or hear very well and was fed via feeding tube. His vision and cognitive function were also impaired.

The plaintiff claimed that the intubation tube should have been adjusted or removed and re-inserted in the ambulance, but that did not happen. At trial, they called as an adverse witness the EMT-paramedic who had been in the ambulance with the plaintiff.

Continue for the outcome >>

OUTCOME  
During the plaintiff’s presentation of evidence, the hospital agreed to a settlement of $13 million. The trial against Dr S. continued but ended in a mistrial. The plaintiffs were expected to re-try the claims against him.

COMMENT  
This is a bad-airway case. Many medical malpractice cases are bad-airways cases: They are easy to bring and easy for jurors to understand, since hypoxic/anoxic injury is evident and plainly correlated with the airway missteps. These cases are also easy to prove, since the plaintiff can always hire an expert to testify that a reasonably prudent clinician would have been able to properly secure and monitor the airway—and the patient “would be standing here today,” unscathed.

Of course, securing an airway is not a “given” and can be challenging. Factor in variables such as anatomy, age, body habitus, intoxication, combativeness, medical comorbidities, and a full stomach, and the risk swells. If your employment requires that you manage airways, you are practicing in a high-legal-risk environment.

Make sure your skills are up to par. Practice often. Have a plan, a backup plan, and rescue backup plan. Have working suction ready. Check your equipment regularly. Run practice codes—particularly if your practice does not manage cardiorespiratory emergencies often. Does your staff know how to open the crash cart? Are the meds expired? Is the oxygen cylinder empty? Are roles clearly defined? As clinicians, we sit through our share of useless meetings (discussing things like who left what in the break room fridge). We should find time to drill on cardiorespiratory emergencies, because there is no time to “reacquaint oneself” on the fly.

In the case report, we are told that the patient was monitored by O₂ saturation (SaO₂) and end tidal CO₂ (ETCO₂). The plaintiff alleges that the transport team (EMT-paramedic and RN) failed to address tube placement and rather focused their efforts on chest compressions and medications. As we know, most cases of pediatric cardiac arrest are not primarily cardiac but instead follow primary progressive respiratory failure. Despite the emphasis on “airway, breathing, circulation” covered by PALS, the airway appears to have been missed and tube placement unquestioned after the child began to decompensate. Tube placement wasn’t reconsidered until 10 minutes after arrival at the second hospital, when the patient was reintubated and ventilatory status improved.

Airway cases—this one included—are “high damages” cases. A high damages case is one in which the injury is clear and expenses and costs to care for the patient are clear and immense. Such cases can be difficult to defend, because the enormity of the plaintiff’s plight (the limitations, years of required rehabilitation, hospitalization, PT, OT, nutritional care, etc) can overwhelm the jury, who may infer negligence based on the plaintiff’s condition. While jurors are required to consider damages only after negligence has been proven, lay jurors are human and many find it difficult to parse liability from damages. This is particularly true in airway cases involving a young, now-debilitated patient and an expert witness claiming an error that was preventable.

In this case, the plaintiff’s attorney made an unusual move, by calling as a “hostile witness” the paramedic who treated the 3-month-old boy. The paramedic would generally be called by the defense and later cross-examined by the plaintiff. Instead, the plaintiff chose to examine him first. Under evidence rules in most states (including North Carolina,¹ where this case was heard), an adverse (or hostile) witness can be called by the opposing party.

Why is this important? Because during direct examination, you cannot lead the witness; during cross-examination, you can. Leading questions (if done correctly) generally produce the most effective and damaging moments during a trial. In this case, the plaintiffs were able to immediately examine one of the defendant’s principal actors using leading questions. Shortly thereafter, when the plaintiff was directly examining his own paramedic expert witnesses, the defense relented and settled for $13 million, with further recovery against the emergency physician still available.

Interestingly, the attorney suing the medical personnel in this case was none other than John Edwards. Yes, that John Edwards—the former vice presidential candidate famous for his $500 haircuts, campaign finance tribulations, and ethical lapses. He originally became famous (and rich) suing clinicians. After his political fall from grace, he is back in business suing clinicians—and for him, business is good.

IN SUM
This case was unfortunate. Always use care in securing the airway, particularly during patient movement. Once it is established, monitor the airway using SaO₂, ETCO₂, and keen observation. Airways are not in the “set it and forget it” camp. An airway must be maintained, safeguarded, and protected. Be prepared to act quickly should the airway become dislodged, migrate, or otherwise fail. —DML

REFERENCE
1. North Carolina Rules of Evidence Rule 611 (1983, c. 701, s. 1.).

A 3-month-old boy was diagnosed with severe respiratory syncytial virus infection at a North Carolina hospital in 2009. The infant was intubated, and a transfer to another hospital that had a pediatric ICU was ordered. The second hospital’s emergency transport service facilitated the transfer.

The ambulance was staffed by an EMT-paramedic and a transport registered nurse, both certified in Pediatric Advanced Life Support (PALS). During transport, the infant was intubated and medically paralyzed with vecuronium. About 10 minutes prior to arrival, the infant’s condition worsened, and he experienced cardiac arrest. Chest compressions and heart medications were provided.

Upon arrival at the second hospital, the infant was resuscitated. An emergency department physician, Dr S., ordered reintubation, and the infant again experienced cardiac arrest. For the next 10 minutes, Dr S. ordered chest compressions and heart medication; he eventually reintubated the infant, at which point cardiac arrest ceased with a spontaneous heartbeat.

After transfer to the pediatric ICU, the infant was diagnosed with permanent hypoxic ischemic brain injury caused by the cardiac episodes and low oxygen intake. At the time of trial, the child could not walk, talk, or hear very well and was fed via feeding tube. His vision and cognitive function were also impaired.

The plaintiff claimed that the intubation tube should have been adjusted or removed and re-inserted in the ambulance, but that did not happen. At trial, they called as an adverse witness the EMT-paramedic who had been in the ambulance with the plaintiff.

Continue for the outcome >>

OUTCOME  
During the plaintiff’s presentation of evidence, the hospital agreed to a settlement of $13 million. The trial against Dr S. continued but ended in a mistrial. The plaintiffs were expected to re-try the claims against him.

COMMENT  
This is a bad-airway case. Many medical malpractice cases are bad-airways cases: They are easy to bring and easy for jurors to understand, since hypoxic/anoxic injury is evident and plainly correlated with the airway missteps. These cases are also easy to prove, since the plaintiff can always hire an expert to testify that a reasonably prudent clinician would have been able to properly secure and monitor the airway—and the patient “would be standing here today,” unscathed.

Of course, securing an airway is not a “given” and can be challenging. Factor in variables such as anatomy, age, body habitus, intoxication, combativeness, medical comorbidities, and a full stomach, and the risk swells. If your employment requires that you manage airways, you are practicing in a high-legal-risk environment.

Make sure your skills are up to par. Practice often. Have a plan, a backup plan, and rescue backup plan. Have working suction ready. Check your equipment regularly. Run practice codes—particularly if your practice does not manage cardiorespiratory emergencies often. Does your staff know how to open the crash cart? Are the meds expired? Is the oxygen cylinder empty? Are roles clearly defined? As clinicians, we sit through our share of useless meetings (discussing things like who left what in the break room fridge). We should find time to drill on cardiorespiratory emergencies, because there is no time to “reacquaint oneself” on the fly.

In the case report, we are told that the patient was monitored by O₂ saturation (SaO₂) and end tidal CO₂ (ETCO₂). The plaintiff alleges that the transport team (EMT-paramedic and RN) failed to address tube placement and rather focused their efforts on chest compressions and medications. As we know, most cases of pediatric cardiac arrest are not primarily cardiac but instead follow primary progressive respiratory failure. Despite the emphasis on “airway, breathing, circulation” covered by PALS, the airway appears to have been missed and tube placement unquestioned after the child began to decompensate. Tube placement wasn’t reconsidered until 10 minutes after arrival at the second hospital, when the patient was reintubated and ventilatory status improved.

Airway cases—this one included—are “high damages” cases. A high damages case is one in which the injury is clear and expenses and costs to care for the patient are clear and immense. Such cases can be difficult to defend, because the enormity of the plaintiff’s plight (the limitations, years of required rehabilitation, hospitalization, PT, OT, nutritional care, etc) can overwhelm the jury, who may infer negligence based on the plaintiff’s condition. While jurors are required to consider damages only after negligence has been proven, lay jurors are human and many find it difficult to parse liability from damages. This is particularly true in airway cases involving a young, now-debilitated patient and an expert witness claiming an error that was preventable.

In this case, the plaintiff’s attorney made an unusual move, by calling as a “hostile witness” the paramedic who treated the 3-month-old boy. The paramedic would generally be called by the defense and later cross-examined by the plaintiff. Instead, the plaintiff chose to examine him first. Under evidence rules in most states (including North Carolina,¹ where this case was heard), an adverse (or hostile) witness can be called by the opposing party.

Why is this important? Because during direct examination, you cannot lead the witness; during cross-examination, you can. Leading questions (if done correctly) generally produce the most effective and damaging moments during a trial. In this case, the plaintiffs were able to immediately examine one of the defendant’s principal actors using leading questions. Shortly thereafter, when the plaintiff was directly examining his own paramedic expert witnesses, the defense relented and settled for $13 million, with further recovery against the emergency physician still available.

Interestingly, the attorney suing the medical personnel in this case was none other than John Edwards. Yes, that John Edwards—the former vice presidential candidate famous for his $500 haircuts, campaign finance tribulations, and ethical lapses. He originally became famous (and rich) suing clinicians. After his political fall from grace, he is back in business suing clinicians—and for him, business is good.

IN SUM
This case was unfortunate. Always use care in securing the airway, particularly during patient movement. Once it is established, monitor the airway using SaO₂, ETCO₂, and keen observation. Airways are not in the “set it and forget it” camp. An airway must be maintained, safeguarded, and protected. Be prepared to act quickly should the airway become dislodged, migrate, or otherwise fail. —DML

REFERENCE
1. North Carolina Rules of Evidence Rule 611 (1983, c. 701, s. 1.).

A 3-month-old boy was diagnosed with severe respiratory syncytial virus infection at a North Carolina hospital in 2009. The infant was intubated, and a transfer to another hospital that had a pediatric ICU was ordered. The second hospital’s emergency transport service facilitated the transfer.

The ambulance was staffed by an EMT-paramedic and a transport registered nurse, both certified in Pediatric Advanced Life Support (PALS). During transport, the infant was intubated and medically paralyzed with vecuronium. About 10 minutes prior to arrival, the infant’s condition worsened, and he experienced cardiac arrest. Chest compressions and heart medications were provided.

Upon arrival at the second hospital, the infant was resuscitated. An emergency department physician, Dr S., ordered reintubation, and the infant again experienced cardiac arrest. For the next 10 minutes, Dr S. ordered chest compressions and heart medication; he eventually reintubated the infant, at which point cardiac arrest ceased with a spontaneous heartbeat.

After transfer to the pediatric ICU, the infant was diagnosed with permanent hypoxic ischemic brain injury caused by the cardiac episodes and low oxygen intake. At the time of trial, the child could not walk, talk, or hear very well and was fed via feeding tube. His vision and cognitive function were also impaired.

The plaintiff claimed that the intubation tube should have been adjusted or removed and re-inserted in the ambulance, but that did not happen. At trial, they called as an adverse witness the EMT-paramedic who had been in the ambulance with the plaintiff.

Continue for the outcome >>

OUTCOME  
During the plaintiff’s presentation of evidence, the hospital agreed to a settlement of $13 million. The trial against Dr S. continued but ended in a mistrial. The plaintiffs were expected to re-try the claims against him.

COMMENT  
This is a bad-airway case. Many medical malpractice cases are bad-airways cases: They are easy to bring and easy for jurors to understand, since hypoxic/anoxic injury is evident and plainly correlated with the airway missteps. These cases are also easy to prove, since the plaintiff can always hire an expert to testify that a reasonably prudent clinician would have been able to properly secure and monitor the airway—and the patient “would be standing here today,” unscathed.

Of course, securing an airway is not a “given” and can be challenging. Factor in variables such as anatomy, age, body habitus, intoxication, combativeness, medical comorbidities, and a full stomach, and the risk swells. If your employment requires that you manage airways, you are practicing in a high-legal-risk environment.

Make sure your skills are up to par. Practice often. Have a plan, a backup plan, and rescue backup plan. Have working suction ready. Check your equipment regularly. Run practice codes—particularly if your practice does not manage cardiorespiratory emergencies often. Does your staff know how to open the crash cart? Are the meds expired? Is the oxygen cylinder empty? Are roles clearly defined? As clinicians, we sit through our share of useless meetings (discussing things like who left what in the break room fridge). We should find time to drill on cardiorespiratory emergencies, because there is no time to “reacquaint oneself” on the fly.

In the case report, we are told that the patient was monitored by O₂ saturation (SaO₂) and end tidal CO₂ (ETCO₂). The plaintiff alleges that the transport team (EMT-paramedic and RN) failed to address tube placement and rather focused their efforts on chest compressions and medications. As we know, most cases of pediatric cardiac arrest are not primarily cardiac but instead follow primary progressive respiratory failure. Despite the emphasis on “airway, breathing, circulation” covered by PALS, the airway appears to have been missed and tube placement unquestioned after the child began to decompensate. Tube placement wasn’t reconsidered until 10 minutes after arrival at the second hospital, when the patient was reintubated and ventilatory status improved.

Airway cases—this one included—are “high damages” cases. A high damages case is one in which the injury is clear and expenses and costs to care for the patient are clear and immense. Such cases can be difficult to defend, because the enormity of the plaintiff’s plight (the limitations, years of required rehabilitation, hospitalization, PT, OT, nutritional care, etc) can overwhelm the jury, who may infer negligence based on the plaintiff’s condition. While jurors are required to consider damages only after negligence has been proven, lay jurors are human and many find it difficult to parse liability from damages. This is particularly true in airway cases involving a young, now-debilitated patient and an expert witness claiming an error that was preventable.

In this case, the plaintiff’s attorney made an unusual move, by calling as a “hostile witness” the paramedic who treated the 3-month-old boy. The paramedic would generally be called by the defense and later cross-examined by the plaintiff. Instead, the plaintiff chose to examine him first. Under evidence rules in most states (including North Carolina,¹ where this case was heard), an adverse (or hostile) witness can be called by the opposing party.

Why is this important? Because during direct examination, you cannot lead the witness; during cross-examination, you can. Leading questions (if done correctly) generally produce the most effective and damaging moments during a trial. In this case, the plaintiffs were able to immediately examine one of the defendant’s principal actors using leading questions. Shortly thereafter, when the plaintiff was directly examining his own paramedic expert witnesses, the defense relented and settled for $13 million, with further recovery against the emergency physician still available.

Interestingly, the attorney suing the medical personnel in this case was none other than John Edwards. Yes, that John Edwards—the former vice presidential candidate famous for his $500 haircuts, campaign finance tribulations, and ethical lapses. He originally became famous (and rich) suing clinicians. After his political fall from grace, he is back in business suing clinicians—and for him, business is good.

IN SUM
This case was unfortunate. Always use care in securing the airway, particularly during patient movement. Once it is established, monitor the airway using SaO₂, ETCO₂, and keen observation. Airways are not in the “set it and forget it” camp. An airway must be maintained, safeguarded, and protected. Be prepared to act quickly should the airway become dislodged, migrate, or otherwise fail. —DML

REFERENCE
1. North Carolina Rules of Evidence Rule 611 (1983, c. 701, s. 1.).