Although the effects of vitamin K on blood coagulation are well-established, it is now clear that many extracellular proteins are carboxylated in a vitamin K-dependent manner, including bone matrix proteins such as osteocalcin and matrix gla protein. Previous studies have reported a relationship between vitamin K levels and bone density and fracture risk. However, optimal circulating vitamin K levels for skeletal health remain unknown. In this cross-sectional study of 374 women with post-menopausal osteoporosis, the authors assessed the relationship between vitamin K levels, vitamin K dependent bone-relevant circulating proteins, bone density, and fractures. In doing so, it was noted that women with prevalent fractures showed lower vitamin K levels than those without fractures. No relationship between vitamin K levels and bone density was noted. Interestingly, different serum levels of vitamin K were associated with optimal carboxylation of different vitamin K-dependent proteins: lower vitamin K levels are needed to support clotting factors than bone matrix proteins. Overall, this study suggests that higher intake is needed to obtain the full skeletal benefit of vitamin K versus its effects on coagulation. Future prospective studies are needed to test this intriguing hypothesis, and to further explore the relationship between vitamin K and bone quality.

For over 20 years, bisphosphonates have been first line therapy to increase bone density and reduce fracture risk in patients with osteoporosis. At present, multiple oral and intravenous bisphosphonates are approved for this indication by regulatory agencies worldwide. Several ‘next-generation’ bisphosphonates with optimized anti-resorptive and pharmacokinetic properties have been developed. Of these agents, minodronate is a particularly potent, third generation azaryl bisphosphonate that is currently approved for osteoporosis treatment in Japan. In this meta-analysis of 13 randomized controlled trials, the effects of minodronate were assessed versus other commonly-used osteoporosis medications. Compared with other drugs (alendronate, risedronate, raloxifene, or eldecalcitol), minodronate more potently suppressed serum bone resorption markers (NTX and TRAcP-5b) and, because bone formation and resorption are coupled, more potently suppressed the bone formation marker bone-specific alkaline phosphatase. In addition to these effects on serum markers, minodronate reduced vertebral fractures more than other medications. Across studies, no differences were noted between minodronate and comparators at the level of bone mineral density. Minodronate treatment is associated with a high incidence of gastrointestinal adverse effects than comparator medications. Taken together, these findings suggest that minodronate represents a potent, orally-available bisphosphonate for vertebral fracture reduction in patients with osteoporosis in Japan.

Chronic obstructive pulmonary disease (COPD) is well-known to be a risk factor for osteoporosis and fragility fractures. However, the interplay between inhaled corticosteroid use in COPD and skeletal outcomes remains unclear. While systemic glucocorticoid therapy clearly impairs bone mass and increases fracture risk, whether inhaled steroids have similar effects remain unknown. Furthermore, since inhaled corticosteroids can reduce lung inflammation and COPD flares, it is possible that, by controlling pulmonary disease, these agents may actually promote bone health. In this real-world retrospective Swedish cohort study, 9,651 COPD patients and 59,454 reference controls were identified. Matching using propensity scoring was performed to identify two populations (COPD and control) with similar characteristics other than the presence of COPD. As expected, COPD patients showed an increased rate of osteoporosis-related events versus controls over approximately 5 years of subsequent follow-up. Amongst COPD patients, high-dose inhaled corticosteroid treatment also increased risk of osteoporosis-related events compared to COPD patients on no or low-dose inhaled steroids. These findings confirm the known relationship between COPD and fracture risk, and suggest that extra attention should be paid to fracture risk in COPD patients receiving high-dose inhaled corticosteroids.

Wrist fractures are common in patients with osteoporosis. In addition to causing pain and triggering functional decline, the presence of a wrist fracture indicates an increased risk of additional fragility fractures in the near future. Most wrist fractures occur in the ultradistal radius, a skeletal site rich in trabecular bone. In contrast, wrist bone density by DXA is most commonly reported in the distal 1/3 radius, a region of the radius with more cortical bone. Abaloparatide is a PTHrP analog that increases bone density and reduces fracture risk. In this sub-analysis of the ACTIVE and ACTIVExtend randomized clinical trial, the effects of abaloparatide on wrist fractures and BMD at various regions of the wrist were assessed. Compared to placebo, abaloparatide treatment significantly increased ultradistal wrist BMD after 18 months of therapy. These gains were preserved during the subsequent extension study when patients were maintained on alendronate. Very few wrist fractures were noted during this study thus precluding robust statistical analysis of the effects of abaloparatide on wrist fracture risk. However, numerically fewer wrist fractures were noted in abaloparatide-treated patients versus controls. Taken together, these results highlight the potential importance of measuring ultradistal radius BMD for patients undergoing therapy with bone anabolic agents. Future studies are needed to better standardize methods for obtaining ultradistal radius BMD measurements and to define least significant change thresholds at this potentially-important skeletal site.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Although the effects of vitamin K on blood coagulation are well-established, it is now clear that many extracellular proteins are carboxylated in a vitamin K-dependent manner, including bone matrix proteins such as osteocalcin and matrix gla protein. Previous studies have reported a relationship between vitamin K levels and bone density and fracture risk. However, optimal circulating vitamin K levels for skeletal health remain unknown. In this cross-sectional study of 374 women with post-menopausal osteoporosis, the authors assessed the relationship between vitamin K levels, vitamin K dependent bone-relevant circulating proteins, bone density, and fractures. In doing so, it was noted that women with prevalent fractures showed lower vitamin K levels than those without fractures. No relationship between vitamin K levels and bone density was noted. Interestingly, different serum levels of vitamin K were associated with optimal carboxylation of different vitamin K-dependent proteins: lower vitamin K levels are needed to support clotting factors than bone matrix proteins. Overall, this study suggests that higher intake is needed to obtain the full skeletal benefit of vitamin K versus its effects on coagulation. Future prospective studies are needed to test this intriguing hypothesis, and to further explore the relationship between vitamin K and bone quality.

For over 20 years, bisphosphonates have been first line therapy to increase bone density and reduce fracture risk in patients with osteoporosis. At present, multiple oral and intravenous bisphosphonates are approved for this indication by regulatory agencies worldwide. Several ‘next-generation’ bisphosphonates with optimized anti-resorptive and pharmacokinetic properties have been developed. Of these agents, minodronate is a particularly potent, third generation azaryl bisphosphonate that is currently approved for osteoporosis treatment in Japan. In this meta-analysis of 13 randomized controlled trials, the effects of minodronate were assessed versus other commonly-used osteoporosis medications. Compared with other drugs (alendronate, risedronate, raloxifene, or eldecalcitol), minodronate more potently suppressed serum bone resorption markers (NTX and TRAcP-5b) and, because bone formation and resorption are coupled, more potently suppressed the bone formation marker bone-specific alkaline phosphatase. In addition to these effects on serum markers, minodronate reduced vertebral fractures more than other medications. Across studies, no differences were noted between minodronate and comparators at the level of bone mineral density. Minodronate treatment is associated with a high incidence of gastrointestinal adverse effects than comparator medications. Taken together, these findings suggest that minodronate represents a potent, orally-available bisphosphonate for vertebral fracture reduction in patients with osteoporosis in Japan.

Chronic obstructive pulmonary disease (COPD) is well-known to be a risk factor for osteoporosis and fragility fractures. However, the interplay between inhaled corticosteroid use in COPD and skeletal outcomes remains unclear. While systemic glucocorticoid therapy clearly impairs bone mass and increases fracture risk, whether inhaled steroids have similar effects remain unknown. Furthermore, since inhaled corticosteroids can reduce lung inflammation and COPD flares, it is possible that, by controlling pulmonary disease, these agents may actually promote bone health. In this real-world retrospective Swedish cohort study, 9,651 COPD patients and 59,454 reference controls were identified. Matching using propensity scoring was performed to identify two populations (COPD and control) with similar characteristics other than the presence of COPD. As expected, COPD patients showed an increased rate of osteoporosis-related events versus controls over approximately 5 years of subsequent follow-up. Amongst COPD patients, high-dose inhaled corticosteroid treatment also increased risk of osteoporosis-related events compared to COPD patients on no or low-dose inhaled steroids. These findings confirm the known relationship between COPD and fracture risk, and suggest that extra attention should be paid to fracture risk in COPD patients receiving high-dose inhaled corticosteroids.

Wrist fractures are common in patients with osteoporosis. In addition to causing pain and triggering functional decline, the presence of a wrist fracture indicates an increased risk of additional fragility fractures in the near future. Most wrist fractures occur in the ultradistal radius, a skeletal site rich in trabecular bone. In contrast, wrist bone density by DXA is most commonly reported in the distal 1/3 radius, a region of the radius with more cortical bone. Abaloparatide is a PTHrP analog that increases bone density and reduces fracture risk. In this sub-analysis of the ACTIVE and ACTIVExtend randomized clinical trial, the effects of abaloparatide on wrist fractures and BMD at various regions of the wrist were assessed. Compared to placebo, abaloparatide treatment significantly increased ultradistal wrist BMD after 18 months of therapy. These gains were preserved during the subsequent extension study when patients were maintained on alendronate. Very few wrist fractures were noted during this study thus precluding robust statistical analysis of the effects of abaloparatide on wrist fracture risk. However, numerically fewer wrist fractures were noted in abaloparatide-treated patients versus controls. Taken together, these results highlight the potential importance of measuring ultradistal radius BMD for patients undergoing therapy with bone anabolic agents. Future studies are needed to better standardize methods for obtaining ultradistal radius BMD measurements and to define least significant change thresholds at this potentially-important skeletal site.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Although the effects of vitamin K on blood coagulation are well-established, it is now clear that many extracellular proteins are carboxylated in a vitamin K-dependent manner, including bone matrix proteins such as osteocalcin and matrix gla protein. Previous studies have reported a relationship between vitamin K levels and bone density and fracture risk. However, optimal circulating vitamin K levels for skeletal health remain unknown. In this cross-sectional study of 374 women with post-menopausal osteoporosis, the authors assessed the relationship between vitamin K levels, vitamin K dependent bone-relevant circulating proteins, bone density, and fractures. In doing so, it was noted that women with prevalent fractures showed lower vitamin K levels than those without fractures. No relationship between vitamin K levels and bone density was noted. Interestingly, different serum levels of vitamin K were associated with optimal carboxylation of different vitamin K-dependent proteins: lower vitamin K levels are needed to support clotting factors than bone matrix proteins. Overall, this study suggests that higher intake is needed to obtain the full skeletal benefit of vitamin K versus its effects on coagulation. Future prospective studies are needed to test this intriguing hypothesis, and to further explore the relationship between vitamin K and bone quality.

For over 20 years, bisphosphonates have been first line therapy to increase bone density and reduce fracture risk in patients with osteoporosis. At present, multiple oral and intravenous bisphosphonates are approved for this indication by regulatory agencies worldwide. Several ‘next-generation’ bisphosphonates with optimized anti-resorptive and pharmacokinetic properties have been developed. Of these agents, minodronate is a particularly potent, third generation azaryl bisphosphonate that is currently approved for osteoporosis treatment in Japan. In this meta-analysis of 13 randomized controlled trials, the effects of minodronate were assessed versus other commonly-used osteoporosis medications. Compared with other drugs (alendronate, risedronate, raloxifene, or eldecalcitol), minodronate more potently suppressed serum bone resorption markers (NTX and TRAcP-5b) and, because bone formation and resorption are coupled, more potently suppressed the bone formation marker bone-specific alkaline phosphatase. In addition to these effects on serum markers, minodronate reduced vertebral fractures more than other medications. Across studies, no differences were noted between minodronate and comparators at the level of bone mineral density. Minodronate treatment is associated with a high incidence of gastrointestinal adverse effects than comparator medications. Taken together, these findings suggest that minodronate represents a potent, orally-available bisphosphonate for vertebral fracture reduction in patients with osteoporosis in Japan.

Chronic obstructive pulmonary disease (COPD) is well-known to be a risk factor for osteoporosis and fragility fractures. However, the interplay between inhaled corticosteroid use in COPD and skeletal outcomes remains unclear. While systemic glucocorticoid therapy clearly impairs bone mass and increases fracture risk, whether inhaled steroids have similar effects remain unknown. Furthermore, since inhaled corticosteroids can reduce lung inflammation and COPD flares, it is possible that, by controlling pulmonary disease, these agents may actually promote bone health. In this real-world retrospective Swedish cohort study, 9,651 COPD patients and 59,454 reference controls were identified. Matching using propensity scoring was performed to identify two populations (COPD and control) with similar characteristics other than the presence of COPD. As expected, COPD patients showed an increased rate of osteoporosis-related events versus controls over approximately 5 years of subsequent follow-up. Amongst COPD patients, high-dose inhaled corticosteroid treatment also increased risk of osteoporosis-related events compared to COPD patients on no or low-dose inhaled steroids. These findings confirm the known relationship between COPD and fracture risk, and suggest that extra attention should be paid to fracture risk in COPD patients receiving high-dose inhaled corticosteroids.

Wrist fractures are common in patients with osteoporosis. In addition to causing pain and triggering functional decline, the presence of a wrist fracture indicates an increased risk of additional fragility fractures in the near future. Most wrist fractures occur in the ultradistal radius, a skeletal site rich in trabecular bone. In contrast, wrist bone density by DXA is most commonly reported in the distal 1/3 radius, a region of the radius with more cortical bone. Abaloparatide is a PTHrP analog that increases bone density and reduces fracture risk. In this sub-analysis of the ACTIVE and ACTIVExtend randomized clinical trial, the effects of abaloparatide on wrist fractures and BMD at various regions of the wrist were assessed. Compared to placebo, abaloparatide treatment significantly increased ultradistal wrist BMD after 18 months of therapy. These gains were preserved during the subsequent extension study when patients were maintained on alendronate. Very few wrist fractures were noted during this study thus precluding robust statistical analysis of the effects of abaloparatide on wrist fracture risk. However, numerically fewer wrist fractures were noted in abaloparatide-treated patients versus controls. Taken together, these results highlight the potential importance of measuring ultradistal radius BMD for patients undergoing therapy with bone anabolic agents. Future studies are needed to better standardize methods for obtaining ultradistal radius BMD measurements and to define least significant change thresholds at this potentially-important skeletal site.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Key clinical point: Hypogonadism is a major risk factor for the development of fractures in men and women treated with glucocorticoid (GC).

Major finding: Major risk factors for vertebral fracture were hypogonadism (odds ratio [OR], 12.38; P = .01) and receiving GC boluses (OR 3.45; P = .01) and that for friability fracture were hypogonadism (OR, 7.03; P = .01) and a FRAX index greater than 20 (OR, 7.08; P = .02).

Study details: A cross-sectional study of 127 adults receiving chronic GC treatment for a rheumatological autoimmune disease.

Disclosures: This study was funded in part by the Societat Catalana de Reumatologia. The authors declared no conflicts of interest.

Citation: Florez H et al. RMD Open. 2020 Sep 10. doi: 10.1136/rmdopen-2020-001355.

Key clinical point: Hypogonadism is a major risk factor for the development of fractures in men and women treated with glucocorticoid (GC).

Major finding: Major risk factors for vertebral fracture were hypogonadism (odds ratio [OR], 12.38; P = .01) and receiving GC boluses (OR 3.45; P = .01) and that for friability fracture were hypogonadism (OR, 7.03; P = .01) and a FRAX index greater than 20 (OR, 7.08; P = .02).

Study details: A cross-sectional study of 127 adults receiving chronic GC treatment for a rheumatological autoimmune disease.

Disclosures: This study was funded in part by the Societat Catalana de Reumatologia. The authors declared no conflicts of interest.

Citation: Florez H et al. RMD Open. 2020 Sep 10. doi: 10.1136/rmdopen-2020-001355.

Key clinical point: Hypogonadism is a major risk factor for the development of fractures in men and women treated with glucocorticoid (GC).

Major finding: Major risk factors for vertebral fracture were hypogonadism (odds ratio [OR], 12.38; P = .01) and receiving GC boluses (OR 3.45; P = .01) and that for friability fracture were hypogonadism (OR, 7.03; P = .01) and a FRAX index greater than 20 (OR, 7.08; P = .02).

Study details: A cross-sectional study of 127 adults receiving chronic GC treatment for a rheumatological autoimmune disease.

Disclosures: This study was funded in part by the Societat Catalana de Reumatologia. The authors declared no conflicts of interest.

Citation: Florez H et al. RMD Open. 2020 Sep 10. doi: 10.1136/rmdopen-2020-001355.

Key clinical point: Abaloparatide/alendronate treatment shows numerically lower risks for wrist fractures compared with placebo/alendronate, suggesting a potential correlation between ultradistal (UD) radius bone mineral density (BMD) and wrist fracture.

Major finding: BMD gains at the UD radius following treatment with abaloparatide in ACTIVE were maintained over the subsequent 24 months of treatment with alendronate in ACTIVExtend (cumulative month 43 treatment difference, 0.89%; P = .20). Conversely, UD radius BMD in the placebo group during ACTIVE decreased to below ACTIVE baseline.

Study details: The data come from a subanalysis of the phase 3 ACTIVExtend trial.

Disclosures: Funding for this study was provided by Radius Health, Inc. NB Watts, RK Dore, and MS LeBoff reported ties with various pharmaceutical companies. B Mitlak and Y Wang were employees of and own company stock in Radius Health, Inc. G Hattersley was a former employee of and a consultant to Radius Health, Inc. TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online. S Baim reported no conflicts of interest.

Citation: Watts NB et al. Osteoporos Int. 2020 Sep 15. doi: 10.1007/s00198-020-05555-1.

Key clinical point: Abaloparatide/alendronate treatment shows numerically lower risks for wrist fractures compared with placebo/alendronate, suggesting a potential correlation between ultradistal (UD) radius bone mineral density (BMD) and wrist fracture.

Major finding: BMD gains at the UD radius following treatment with abaloparatide in ACTIVE were maintained over the subsequent 24 months of treatment with alendronate in ACTIVExtend (cumulative month 43 treatment difference, 0.89%; P = .20). Conversely, UD radius BMD in the placebo group during ACTIVE decreased to below ACTIVE baseline.

Study details: The data come from a subanalysis of the phase 3 ACTIVExtend trial.

Disclosures: Funding for this study was provided by Radius Health, Inc. NB Watts, RK Dore, and MS LeBoff reported ties with various pharmaceutical companies. B Mitlak and Y Wang were employees of and own company stock in Radius Health, Inc. G Hattersley was a former employee of and a consultant to Radius Health, Inc. TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online. S Baim reported no conflicts of interest.

Citation: Watts NB et al. Osteoporos Int. 2020 Sep 15. doi: 10.1007/s00198-020-05555-1.

Key clinical point: Abaloparatide/alendronate treatment shows numerically lower risks for wrist fractures compared with placebo/alendronate, suggesting a potential correlation between ultradistal (UD) radius bone mineral density (BMD) and wrist fracture.

Major finding: BMD gains at the UD radius following treatment with abaloparatide in ACTIVE were maintained over the subsequent 24 months of treatment with alendronate in ACTIVExtend (cumulative month 43 treatment difference, 0.89%; P = .20). Conversely, UD radius BMD in the placebo group during ACTIVE decreased to below ACTIVE baseline.

Study details: The data come from a subanalysis of the phase 3 ACTIVExtend trial.

Disclosures: Funding for this study was provided by Radius Health, Inc. NB Watts, RK Dore, and MS LeBoff reported ties with various pharmaceutical companies. B Mitlak and Y Wang were employees of and own company stock in Radius Health, Inc. G Hattersley was a former employee of and a consultant to Radius Health, Inc. TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online. S Baim reported no conflicts of interest.

Citation: Watts NB et al. Osteoporos Int. 2020 Sep 15. doi: 10.1007/s00198-020-05555-1.

Key clinical point: Use of high-dose inhaled corticosteroids (ICS) significantly increased the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD).

Major finding: Patients with COPD using ICS were at an increased risk for any osteoporosis-related event (high dose: risk ratio [RR], 1.52; 95% confidence interval [CI], 1.24-1.82] and low dose: RR, 1.27; 95% CI, 1.13-1.56) compared with those not using ICS.

Study details: The data come from ARCTIC study of 9,651 patients with COPD and 59,454 matched reference controls.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. C Janson, K Lisspers, B Ställberg, G Johansson, and K Larsson reported relationships with various pharmaceutical companies, including Novartis. FS Gutzwiller and K Mezzi are employees of Novartis. L Mindeholm is a consultant to Novartis Institutes for Biomedical Research and holds stocks in Novartis. BK Bjerregaard and L Jorgensen are employees of IQVIA and have received remuneration in relation to statistical analyses.

Citation: Janson C et al. Eur Respir J. 2020 Sep 24. doi: 10.1183/13993003.00515-2020.

Key clinical point: Use of high-dose inhaled corticosteroids (ICS) significantly increased the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD).

Major finding: Patients with COPD using ICS were at an increased risk for any osteoporosis-related event (high dose: risk ratio [RR], 1.52; 95% confidence interval [CI], 1.24-1.82] and low dose: RR, 1.27; 95% CI, 1.13-1.56) compared with those not using ICS.

Study details: The data come from ARCTIC study of 9,651 patients with COPD and 59,454 matched reference controls.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. C Janson, K Lisspers, B Ställberg, G Johansson, and K Larsson reported relationships with various pharmaceutical companies, including Novartis. FS Gutzwiller and K Mezzi are employees of Novartis. L Mindeholm is a consultant to Novartis Institutes for Biomedical Research and holds stocks in Novartis. BK Bjerregaard and L Jorgensen are employees of IQVIA and have received remuneration in relation to statistical analyses.

Citation: Janson C et al. Eur Respir J. 2020 Sep 24. doi: 10.1183/13993003.00515-2020.

Key clinical point: Use of high-dose inhaled corticosteroids (ICS) significantly increased the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD).

Major finding: Patients with COPD using ICS were at an increased risk for any osteoporosis-related event (high dose: risk ratio [RR], 1.52; 95% confidence interval [CI], 1.24-1.82] and low dose: RR, 1.27; 95% CI, 1.13-1.56) compared with those not using ICS.

Study details: The data come from ARCTIC study of 9,651 patients with COPD and 59,454 matched reference controls.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. C Janson, K Lisspers, B Ställberg, G Johansson, and K Larsson reported relationships with various pharmaceutical companies, including Novartis. FS Gutzwiller and K Mezzi are employees of Novartis. L Mindeholm is a consultant to Novartis Institutes for Biomedical Research and holds stocks in Novartis. BK Bjerregaard and L Jorgensen are employees of IQVIA and have received remuneration in relation to statistical analyses.

Citation: Janson C et al. Eur Respir J. 2020 Sep 24. doi: 10.1183/13993003.00515-2020.

Key clinical point: Minodronate demonstrated better efficacy than alendronate, risedronate, raloxifene, or eldecalcitol in patients with osteoporosis.

Major finding: Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD], −13.669; 95% confidence interval [CI], −23.108 to −4.229), bone alkaline phosphatase (WMD, −1.26; 95% CI: −2.04 to −0.47), and tartrate-resistant acid phosphatase 5b (WMD, −154.11; 95% CI, −277.85 to −30.37).

Study details: A meta-analysis of 13 randomized controlled trials including 3,740 patients with osteoporosis.

Disclosures: This study received no financial support. The authors declared no conflicts of interest.

Citation: Liu Q et al. 2020 Oct 2. doi: 10.1097/MD.0000000000022542.

Key clinical point: Minodronate demonstrated better efficacy than alendronate, risedronate, raloxifene, or eldecalcitol in patients with osteoporosis.

Major finding: Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD], −13.669; 95% confidence interval [CI], −23.108 to −4.229), bone alkaline phosphatase (WMD, −1.26; 95% CI: −2.04 to −0.47), and tartrate-resistant acid phosphatase 5b (WMD, −154.11; 95% CI, −277.85 to −30.37).

Study details: A meta-analysis of 13 randomized controlled trials including 3,740 patients with osteoporosis.

Disclosures: This study received no financial support. The authors declared no conflicts of interest.

Citation: Liu Q et al. 2020 Oct 2. doi: 10.1097/MD.0000000000022542.

Key clinical point: Minodronate demonstrated better efficacy than alendronate, risedronate, raloxifene, or eldecalcitol in patients with osteoporosis.

Major finding: Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD], −13.669; 95% confidence interval [CI], −23.108 to −4.229), bone alkaline phosphatase (WMD, −1.26; 95% CI: −2.04 to −0.47), and tartrate-resistant acid phosphatase 5b (WMD, −154.11; 95% CI, −277.85 to −30.37).

Study details: A meta-analysis of 13 randomized controlled trials including 3,740 patients with osteoporosis.

Disclosures: This study received no financial support. The authors declared no conflicts of interest.

Citation: Liu Q et al. 2020 Oct 2. doi: 10.1097/MD.0000000000022542.

Key clinical point: The risk for moderate coronary artery calcification (CAC) is inversely and independently associated with bone mineral density (BMD) of the lumbar spine in adults with osteoporosis.

Major finding: After adjustments for significant factors of CAC, BMD of the lumbar spine was significantly and inversely associated with moderate CAC in patients with osteoporosis (odds ratio, 0.38; P = .035). However, no association between CAC and BMD was seen in patients with osteopenia.

Study details: The findings are based on a retrospective medical review study of 246 patients (osteoporosis group, n = 52; osteopenia group, n = 194).

Disclosures: The study was funded by Buddhist Tzu Chi Medical Foundation. The authors declared no conflicts of interest.

Citation: Chuang TL et al. Diagnostics (Basel). 2020 Sep 16. doi: 10.3390/diagnostics10090699.

Key clinical point: The risk for moderate coronary artery calcification (CAC) is inversely and independently associated with bone mineral density (BMD) of the lumbar spine in adults with osteoporosis.

Major finding: After adjustments for significant factors of CAC, BMD of the lumbar spine was significantly and inversely associated with moderate CAC in patients with osteoporosis (odds ratio, 0.38; P = .035). However, no association between CAC and BMD was seen in patients with osteopenia.

Study details: The findings are based on a retrospective medical review study of 246 patients (osteoporosis group, n = 52; osteopenia group, n = 194).

Disclosures: The study was funded by Buddhist Tzu Chi Medical Foundation. The authors declared no conflicts of interest.

Citation: Chuang TL et al. Diagnostics (Basel). 2020 Sep 16. doi: 10.3390/diagnostics10090699.

Key clinical point: The risk for moderate coronary artery calcification (CAC) is inversely and independently associated with bone mineral density (BMD) of the lumbar spine in adults with osteoporosis.

Major finding: After adjustments for significant factors of CAC, BMD of the lumbar spine was significantly and inversely associated with moderate CAC in patients with osteoporosis (odds ratio, 0.38; P = .035). However, no association between CAC and BMD was seen in patients with osteopenia.

Study details: The findings are based on a retrospective medical review study of 246 patients (osteoporosis group, n = 52; osteopenia group, n = 194).

Disclosures: The study was funded by Buddhist Tzu Chi Medical Foundation. The authors declared no conflicts of interest.

Citation: Chuang TL et al. Diagnostics (Basel). 2020 Sep 16. doi: 10.3390/diagnostics10090699.

Key clinical point: Metabolic syndrome (MetS) is associated with an increased risk for low bone mineral density (BMD) in women examined by dual-energy X-ray absorptiometry (DXA) for suspected osteoporosis.

Major finding: MetS was associated with an increased risk for low BMD (odds ratio [OR], 1.19; P = .001). Among MetS components, hypertension significantly correlated with an increased risk for low BMD (OR, 1.23; P = .002), whereas high fasting glucose level/diabetes correlated with a reduced occurrence of low BMD (OR, 0.84; P = .003).

Study details: The data come from a cross-sectional study of 13,182 free-living Caucasian women in Italy (mean age, 62.8 years) who underwent diagnostic assessment of BMD by DXA and of all MetS constitutive elements.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Citation: Rendina D et al. J Endocrinol Invest. 2020 Sep 22. doi: 10.1007/s40618-020-01428-w.

Key clinical point: Metabolic syndrome (MetS) is associated with an increased risk for low bone mineral density (BMD) in women examined by dual-energy X-ray absorptiometry (DXA) for suspected osteoporosis.

Major finding: MetS was associated with an increased risk for low BMD (odds ratio [OR], 1.19; P = .001). Among MetS components, hypertension significantly correlated with an increased risk for low BMD (OR, 1.23; P = .002), whereas high fasting glucose level/diabetes correlated with a reduced occurrence of low BMD (OR, 0.84; P = .003).

Study details: The data come from a cross-sectional study of 13,182 free-living Caucasian women in Italy (mean age, 62.8 years) who underwent diagnostic assessment of BMD by DXA and of all MetS constitutive elements.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Citation: Rendina D et al. J Endocrinol Invest. 2020 Sep 22. doi: 10.1007/s40618-020-01428-w.

Key clinical point: Metabolic syndrome (MetS) is associated with an increased risk for low bone mineral density (BMD) in women examined by dual-energy X-ray absorptiometry (DXA) for suspected osteoporosis.

Major finding: MetS was associated with an increased risk for low BMD (odds ratio [OR], 1.19; P = .001). Among MetS components, hypertension significantly correlated with an increased risk for low BMD (OR, 1.23; P = .002), whereas high fasting glucose level/diabetes correlated with a reduced occurrence of low BMD (OR, 0.84; P = .003).

Study details: The data come from a cross-sectional study of 13,182 free-living Caucasian women in Italy (mean age, 62.8 years) who underwent diagnostic assessment of BMD by DXA and of all MetS constitutive elements.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Citation: Rendina D et al. J Endocrinol Invest. 2020 Sep 22. doi: 10.1007/s40618-020-01428-w.

Key clinical point: Higher serum vitamin K1 (phylloquinone) concentration is associated with a reduced risk for fracture in women with postmenopausal osteoporosis (PMO).

Major finding: Serum vitamin K1 was significantly lower in women with prevalent fractures vs. those without (0.53 μg/L vs. 0.65 μg/L; P = .04). Vitamin K1 inversely correlated with fracture risk (adjusted odds ratio per μg/L increase in serum vitamin K1, 0.550; P = .042). Hip geometry and mechanical strength parameters including cross-sectional area, cross-sectional moment of inertia, and section modulus ‘Z’ at the narrow neck of femur were positively associated with vitamin K1.

Study details: The data come from a cross-sectional study of 374 women with PMO (mean age, 68.7 years).

Disclosures: The study was funded, in part, by the Royal Osteoporosis Society, U.K. The authors declared no conflicts of interest.

Citation: Moore AE et al. Bone. 2020 Sep 10. doi: 10.1016/j.bone.2020.115630.

Key clinical point: Higher serum vitamin K1 (phylloquinone) concentration is associated with a reduced risk for fracture in women with postmenopausal osteoporosis (PMO).

Major finding: Serum vitamin K1 was significantly lower in women with prevalent fractures vs. those without (0.53 μg/L vs. 0.65 μg/L; P = .04). Vitamin K1 inversely correlated with fracture risk (adjusted odds ratio per μg/L increase in serum vitamin K1, 0.550; P = .042). Hip geometry and mechanical strength parameters including cross-sectional area, cross-sectional moment of inertia, and section modulus ‘Z’ at the narrow neck of femur were positively associated with vitamin K1.

Study details: The data come from a cross-sectional study of 374 women with PMO (mean age, 68.7 years).

Disclosures: The study was funded, in part, by the Royal Osteoporosis Society, U.K. The authors declared no conflicts of interest.

Citation: Moore AE et al. Bone. 2020 Sep 10. doi: 10.1016/j.bone.2020.115630.

Key clinical point: Higher serum vitamin K1 (phylloquinone) concentration is associated with a reduced risk for fracture in women with postmenopausal osteoporosis (PMO).

Major finding: Serum vitamin K1 was significantly lower in women with prevalent fractures vs. those without (0.53 μg/L vs. 0.65 μg/L; P = .04). Vitamin K1 inversely correlated with fracture risk (adjusted odds ratio per μg/L increase in serum vitamin K1, 0.550; P = .042). Hip geometry and mechanical strength parameters including cross-sectional area, cross-sectional moment of inertia, and section modulus ‘Z’ at the narrow neck of femur were positively associated with vitamin K1.

Study details: The data come from a cross-sectional study of 374 women with PMO (mean age, 68.7 years).

Disclosures: The study was funded, in part, by the Royal Osteoporosis Society, U.K. The authors declared no conflicts of interest.

Citation: Moore AE et al. Bone. 2020 Sep 10. doi: 10.1016/j.bone.2020.115630.

Key clinical point: Patients with osteoporosis with age-related macular degeneration (AMD) are at a significantly higher risk of developing spine and hip fractures.

Major finding: The AMD vs. non-AMD group had a significantly higher risk for spine and hip fractures (hazard ratio [HR], 1.09; P less than .001 and HR, 1.18; P = .001; respectively). The risk for mortality was significantly higher in patients with osteoporosis with older age, male sex, and all types of comorbidities (P less than .05), except for hyperthyroidism (P = .200).

Study details: This Taiwanese nationwide study included 1,206,247 patients with osteoporosis using insurance claims data. After propensity score matching, 13,548 and 54,336 patients were analyzed in the AMD and non-AMD groups, respectively.

Disclosures: The study was supported by Chang Gung Medical Research Foundation. The authors declared no conflicts of interest.

Citation: Sun CC et al. BMJ Open. 2020 Sep 17. doi: 10.1136/bmjopen-2020-037028.

Key clinical point: Patients with osteoporosis with age-related macular degeneration (AMD) are at a significantly higher risk of developing spine and hip fractures.

Major finding: The AMD vs. non-AMD group had a significantly higher risk for spine and hip fractures (hazard ratio [HR], 1.09; P less than .001 and HR, 1.18; P = .001; respectively). The risk for mortality was significantly higher in patients with osteoporosis with older age, male sex, and all types of comorbidities (P less than .05), except for hyperthyroidism (P = .200).

Study details: This Taiwanese nationwide study included 1,206,247 patients with osteoporosis using insurance claims data. After propensity score matching, 13,548 and 54,336 patients were analyzed in the AMD and non-AMD groups, respectively.

Disclosures: The study was supported by Chang Gung Medical Research Foundation. The authors declared no conflicts of interest.

Citation: Sun CC et al. BMJ Open. 2020 Sep 17. doi: 10.1136/bmjopen-2020-037028.

Key clinical point: Patients with osteoporosis with age-related macular degeneration (AMD) are at a significantly higher risk of developing spine and hip fractures.

Major finding: The AMD vs. non-AMD group had a significantly higher risk for spine and hip fractures (hazard ratio [HR], 1.09; P less than .001 and HR, 1.18; P = .001; respectively). The risk for mortality was significantly higher in patients with osteoporosis with older age, male sex, and all types of comorbidities (P less than .05), except for hyperthyroidism (P = .200).

Study details: This Taiwanese nationwide study included 1,206,247 patients with osteoporosis using insurance claims data. After propensity score matching, 13,548 and 54,336 patients were analyzed in the AMD and non-AMD groups, respectively.

Disclosures: The study was supported by Chang Gung Medical Research Foundation. The authors declared no conflicts of interest.

Citation: Sun CC et al. BMJ Open. 2020 Sep 17. doi: 10.1136/bmjopen-2020-037028.

Routinely collected clinical data help identify men with high-risk prostate cancer most likely to benefit from a gallium-68 prostate-specific membrane antigen (PSMA) PET/CT scan, according to a study reported at the American Society for Radiation Oncology Annual Meeting 2020.

Courtesy of University of California Los Angeles

“PSMA PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” noted study investigator T. Martin Ma, MD, PhD, of the University of California, Los Angeles.

The proPSMA trial, published in The Lancet earlier this year, found PSMA PET/CT to be superior to conventional imaging for primary staging of high-risk prostate cancer.

“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma noted.

With the current study, Dr. Ma and colleagues set out to assess the impact of PSMA PET/CT in nodal and metastatic upstaging in patients with high-risk prostate cancer and explore predictors of upstaging.

The researchers conducted a post hoc analysis of a single-center, prospective study of 262 patients with high-risk prostate cancer (cN1 or cN0 on conventional imaging) undergoing primary staging. Patients who had received 3 or more months of androgen deprivation therapy before their scan were excluded.
 

Study results

PSMA PET/CT led to nodal upstaging – from N0 to N1 – in 19.7% of patients and metastasis upstaging – from M0 to M1a, b, or c – in 9.4%.

“It is worth pointing out that the percentage of upstaging at the PSMA scan in our study is very similar to that in the proPSMA study,” Dr. Ma noted, with that trial finding nodal upstaging in 18% of patients and metastasis upstaging in 8%.

In multivariate analysis, independent predictors of nodal upstaging with PSMA PET/CT were higher percentage of positive cores at biopsy (odds ratio per decile, 1.21; P = .001) and higher Gleason grade (OR, 1.61; P = .025).

Similarly, independent predictors of metastasis upstaging were higher percentage of positive cores at biopsy (OR per decile, 1.19; P = .013) and higher Gleason grade (OR, 2.13; P = .024).

Other factors – clinical T stage and N stage, initial prostate-specific antigen level, and presence of two or more high-risk features – did not independently predict these outcomes.

When various combinations were assessed, the incidence of nodal upstaging was highest for patients who had a Gleason grade of 4 or 5 plus at least 50% positive cores (27.5% vs. 13.1% among all others). Similarly, incidence of metastasis upstaging was highest for those who had a Gleason grade of 5 plus at least 50% positive cores (20.6% vs. 5.9% among all others).

“Patients with percent-positive cores of 50% or more and Gleason grade group 4 or 5 will benefit the most from a PSMA PET/CT scan,” Dr. Ma concluded. “Future studies should validate the importance of these factors and identify whether changing treatment leads to improved outcomes.”

“The beauty of percent-positive cores is that it is an objective and routinely available piece of clinical information from systematic biopsy,” he added. “It may aid in the selection of patients in resource-limited settings and consideration of treatment intensification. We may also consider incorporation of percent positive cores into clinical risk stratification schemes for clinical use.”
 

A game changer

“PSMA PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Centre in Melbourne, who was not involved in this study.

“PSMA PET/CT has challenged conventional imaging in staging before curative intent surgery or radiotherapy,” Dr. Eapen added.

Accuracy of PSMA PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview. This superior accuracy can ultimately have management impact, while the imaging has additional benefits of lower radiation dose and reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.

“This prospective study by Ma et al. is a great adjunct to the proPSMA results, with the aims of further stratifying patients who are likely to be upstaged on PSMA PET/CT,” Dr. Eapen said. “As the availability of PSMA PET/CT increases and more centers adopt this technology, we need studies like these to risk-stratify patients and select those who would benefit.”

The study did not receive any specific funding. Dr. Ma and Dr. Eapen disclosed no conflicts of interest.

SOURCE: Ma TM et al. ASTRO 2020, Abstract 58.

Routinely collected clinical data help identify men with high-risk prostate cancer most likely to benefit from a gallium-68 prostate-specific membrane antigen (PSMA) PET/CT scan, according to a study reported at the American Society for Radiation Oncology Annual Meeting 2020.

Courtesy of University of California Los Angeles

“PSMA PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” noted study investigator T. Martin Ma, MD, PhD, of the University of California, Los Angeles.

The proPSMA trial, published in The Lancet earlier this year, found PSMA PET/CT to be superior to conventional imaging for primary staging of high-risk prostate cancer.

“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma noted.

With the current study, Dr. Ma and colleagues set out to assess the impact of PSMA PET/CT in nodal and metastatic upstaging in patients with high-risk prostate cancer and explore predictors of upstaging.

The researchers conducted a post hoc analysis of a single-center, prospective study of 262 patients with high-risk prostate cancer (cN1 or cN0 on conventional imaging) undergoing primary staging. Patients who had received 3 or more months of androgen deprivation therapy before their scan were excluded.
 

Study results

PSMA PET/CT led to nodal upstaging – from N0 to N1 – in 19.7% of patients and metastasis upstaging – from M0 to M1a, b, or c – in 9.4%.

“It is worth pointing out that the percentage of upstaging at the PSMA scan in our study is very similar to that in the proPSMA study,” Dr. Ma noted, with that trial finding nodal upstaging in 18% of patients and metastasis upstaging in 8%.

In multivariate analysis, independent predictors of nodal upstaging with PSMA PET/CT were higher percentage of positive cores at biopsy (odds ratio per decile, 1.21; P = .001) and higher Gleason grade (OR, 1.61; P = .025).

Similarly, independent predictors of metastasis upstaging were higher percentage of positive cores at biopsy (OR per decile, 1.19; P = .013) and higher Gleason grade (OR, 2.13; P = .024).

Other factors – clinical T stage and N stage, initial prostate-specific antigen level, and presence of two or more high-risk features – did not independently predict these outcomes.

When various combinations were assessed, the incidence of nodal upstaging was highest for patients who had a Gleason grade of 4 or 5 plus at least 50% positive cores (27.5% vs. 13.1% among all others). Similarly, incidence of metastasis upstaging was highest for those who had a Gleason grade of 5 plus at least 50% positive cores (20.6% vs. 5.9% among all others).

“Patients with percent-positive cores of 50% or more and Gleason grade group 4 or 5 will benefit the most from a PSMA PET/CT scan,” Dr. Ma concluded. “Future studies should validate the importance of these factors and identify whether changing treatment leads to improved outcomes.”

“The beauty of percent-positive cores is that it is an objective and routinely available piece of clinical information from systematic biopsy,” he added. “It may aid in the selection of patients in resource-limited settings and consideration of treatment intensification. We may also consider incorporation of percent positive cores into clinical risk stratification schemes for clinical use.”
 

A game changer

“PSMA PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Centre in Melbourne, who was not involved in this study.

“PSMA PET/CT has challenged conventional imaging in staging before curative intent surgery or radiotherapy,” Dr. Eapen added.

Accuracy of PSMA PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview. This superior accuracy can ultimately have management impact, while the imaging has additional benefits of lower radiation dose and reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.

“This prospective study by Ma et al. is a great adjunct to the proPSMA results, with the aims of further stratifying patients who are likely to be upstaged on PSMA PET/CT,” Dr. Eapen said. “As the availability of PSMA PET/CT increases and more centers adopt this technology, we need studies like these to risk-stratify patients and select those who would benefit.”

The study did not receive any specific funding. Dr. Ma and Dr. Eapen disclosed no conflicts of interest.

SOURCE: Ma TM et al. ASTRO 2020, Abstract 58.

Routinely collected clinical data help identify men with high-risk prostate cancer most likely to benefit from a gallium-68 prostate-specific membrane antigen (PSMA) PET/CT scan, according to a study reported at the American Society for Radiation Oncology Annual Meeting 2020.

Courtesy of University of California Los Angeles

“PSMA PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” noted study investigator T. Martin Ma, MD, PhD, of the University of California, Los Angeles.

The proPSMA trial, published in The Lancet earlier this year, found PSMA PET/CT to be superior to conventional imaging for primary staging of high-risk prostate cancer.

“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma noted.

With the current study, Dr. Ma and colleagues set out to assess the impact of PSMA PET/CT in nodal and metastatic upstaging in patients with high-risk prostate cancer and explore predictors of upstaging.

The researchers conducted a post hoc analysis of a single-center, prospective study of 262 patients with high-risk prostate cancer (cN1 or cN0 on conventional imaging) undergoing primary staging. Patients who had received 3 or more months of androgen deprivation therapy before their scan were excluded.
 

Study results

PSMA PET/CT led to nodal upstaging – from N0 to N1 – in 19.7% of patients and metastasis upstaging – from M0 to M1a, b, or c – in 9.4%.

“It is worth pointing out that the percentage of upstaging at the PSMA scan in our study is very similar to that in the proPSMA study,” Dr. Ma noted, with that trial finding nodal upstaging in 18% of patients and metastasis upstaging in 8%.

In multivariate analysis, independent predictors of nodal upstaging with PSMA PET/CT were higher percentage of positive cores at biopsy (odds ratio per decile, 1.21; P = .001) and higher Gleason grade (OR, 1.61; P = .025).

Similarly, independent predictors of metastasis upstaging were higher percentage of positive cores at biopsy (OR per decile, 1.19; P = .013) and higher Gleason grade (OR, 2.13; P = .024).

Other factors – clinical T stage and N stage, initial prostate-specific antigen level, and presence of two or more high-risk features – did not independently predict these outcomes.

When various combinations were assessed, the incidence of nodal upstaging was highest for patients who had a Gleason grade of 4 or 5 plus at least 50% positive cores (27.5% vs. 13.1% among all others). Similarly, incidence of metastasis upstaging was highest for those who had a Gleason grade of 5 plus at least 50% positive cores (20.6% vs. 5.9% among all others).

“Patients with percent-positive cores of 50% or more and Gleason grade group 4 or 5 will benefit the most from a PSMA PET/CT scan,” Dr. Ma concluded. “Future studies should validate the importance of these factors and identify whether changing treatment leads to improved outcomes.”

“The beauty of percent-positive cores is that it is an objective and routinely available piece of clinical information from systematic biopsy,” he added. “It may aid in the selection of patients in resource-limited settings and consideration of treatment intensification. We may also consider incorporation of percent positive cores into clinical risk stratification schemes for clinical use.”
 

A game changer

“PSMA PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Centre in Melbourne, who was not involved in this study.

“PSMA PET/CT has challenged conventional imaging in staging before curative intent surgery or radiotherapy,” Dr. Eapen added.

Accuracy of PSMA PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview. This superior accuracy can ultimately have management impact, while the imaging has additional benefits of lower radiation dose and reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.

“This prospective study by Ma et al. is a great adjunct to the proPSMA results, with the aims of further stratifying patients who are likely to be upstaged on PSMA PET/CT,” Dr. Eapen said. “As the availability of PSMA PET/CT increases and more centers adopt this technology, we need studies like these to risk-stratify patients and select those who would benefit.”

The study did not receive any specific funding. Dr. Ma and Dr. Eapen disclosed no conflicts of interest.

SOURCE: Ma TM et al. ASTRO 2020, Abstract 58.