Patterns of Prescription #Drug Use Before and After Fragility #Fracture

http://archinte.jamanetwork.com/mobile/article.aspx?articleid=2544881

Conclusions and Relevance Exposure to prescription drugs associated with fracture risk is infrequently reduced following fragility fracture occurrence. While some patients eliminate their exposure to drugs associated with fracture, an equal number initiate new high-risk drugs. This pattern suggests there is a missed opportunity to modify at least one factor contributing to secondary fractures.

Longer Duration of #Diabetes Strongly Impacts #Fracture Risk Assessment: The Manitoba BMD Cohort

http://press.endocrine.org/doi/abs/10.1210/jc.2016-2569

Summary:
Diabetes is a FRAX-independent risk factor for MOF only in women with long-duration diabetes but diabetes increases hip fracture risk regardless of duration. Those with diabetes >10years are at particularly high risk of fracture, and this elevated risk is currently under-estimated by FRAX.

Association of 3 Different #Antihypertensive Medications With Hip and Pelvic #Fracture Risk in Older Adults

http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2587085

These findings from a large randomized clinical trial provide evidence of a beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic fracture risk compared with treatment with other antihypertensive medications.

Use of #glucose-lowering drugs and risk of #fracture in patients with type 2 diabetes

http://www.sciencedirect.com/science/article/pii/S8756328216303593?via%3Dihub

Current use of sulphonylureas was associated with an increased risk of fracture in both male and female patients.

Current use of glitazones was associated with an increased risk of fracture in both men and women.

Ever use of sulphonylureas was not associated with an increased risk of fracture in patients with type 2 diabetes.

Advanced age, previous major osteoporotic fractures, falls and were all associated with an increased risk of fracture.

The risk of #fracture among patients with psoriatic arthritis and #psoriasis: a population-based study

http://ardbeta.bmj.com/content/early/2017/01/16/annrheumdis-2016-210441

Patients with severe psoriasis had significantly elevated risk of all fracture and vertebral fracture: aHR 1.26 (1.15 to 1.39) and 2.23 (1.54 to 3.22).
PsA and psoriasis are associated with an elevated risk for fracture.

#Alendronate Use and Hip #Fracture Risk in Older Patients Using Oral #Prednisolone
http://jamanetwork.com/journals/jama/article-abstract/2643309

Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids.

The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 95% CI, 11.6-21.0 vs 12.9 95% CI, 9.3-18.0 per 1000 person-years; P = .40) or peptic ulcers (10.9 95% CI, 7.7-15.5 vs 11.4 95% CI, 8.0-16.2 per 1000 person-years; P = .86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group

Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.

The Ability of a Single #BMD and Fracture History Assessment to Predict #Fracture Over 25 Years in Postmenopausal Women: The Study of Osteoporotic Fractures
http://onlinelibrary.wiley.com/doi/10.1002/jbmr.3194/abstract

The ability of bone mineral density (BMD) and other risk factors to predict fracture risk is well-established for as long as 5 to 10 years. However, their value to predict risk over a longer term has not been directly studied. We investigated whether a single assessment of femoral neck BMD and fracture history can predict fracture risk over 20 to 25 years. A single femoral neck BMD measurement strongly predicted long-term hip fracture risk to 25 years: 29.6% risk in the lowest BMD quartile versus 7.6% with the highest relative hazard (RH) = 4.9 (95% CI, 4.1 to 6.0). Femoral neck BMD predicted hip fracture with little degradation over time from RH/SD = 2.6 (2.2 to 3.0) for 0 to 5 years to RH/SD = 1.8 (1.4 to 2.4) for 20 to 25 years. Lifetime hip fracture risk was similar (∼30%) regardless of age from 67 to >80 years. History of hip fracture predicted hip fractures only slightly better than history of nonvertebral fracture

We conclude that a single BMD and fracture history assessment can predict fracture risk over 20 to 25 years. Long-term risk of hip fracture remains extremely high in the oldest age groups, supporting risk assessment and consideration of treatment even in the oldest, highest-risk women

Atypical #fracture with long-term #bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance
http://m.pnas.org/content/early/2017/07/25/1704460114.full

Bisphosphonates are the most widely prescribed pharmacologic treatment for osteoporosis and reduce fracture risk in postmenopausal women by up to 50%. However, in the past decade these drugs have been associated with atypical femoral fractures (AFFs), rare fractures with a transverse, brittle morphology. The unusual fracture morphology suggests that bisphosphonate treatment may impair toughening mechanisms in cortical bone Patients were allocated to five groups based on fracture morphology and history of bisphosphonate treatment +BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; +BIS Typical: n = 10, 7.7 (5.0) y; +BIS Nonfx: n = 5, 6.4 (3.5) y; −BIS Typical: n = 11; −BIS Nonfx: n = 12

fracture mechanics measurements showed that tissue from patients treated with bisphosphonates had deficits in fracture toughness, with lower crack-initiation toughness and less crack deflection at osteonal boundaries than that of bisphosphonate-naïve patients.

Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term bisphosphonates

Association Between #Calcium or Vitamin #D Supplementation and #Fracture Incidence in Community-Dwelling Older Adults A Systematic Review and Meta-analysis

https://jamanetwork.com/journals/jama/article-abstract/2667071?resultClick=1&redirect=true

A total of 33 randomized trials involving 51 145 participants fulfilled the inclusion criteria. There was no significant association of calcium or vitamin D with risk of hip fracture compared with placebo or no treatment (calcium: RR, 1.53 95% CI, 0.97 to 2.42; ARD, 0.01 95% CI, 0.00 to 0.01; vitamin D: RR, 1.21 95% CI, 0.99 to 1.47; ARD, 0.00 95% CI, −0.00 to 0.01. There was no significant association of combined calcium and vitamin D with hip fracture compared with placebo or no treatment (RR, 1.09 95% CI, 0.85 to 1.39; ARD, 0.00 95% CI, −0.00 to 0.00). No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration.

Conclusions and Relevance In this meta-analysis of randomized clinical trials, the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. These findings do not support the routine use of these supplements in community-dwelling older people.

Future Osteoporotic #Fracture Risk Related to Lumbar Vertebral Trabecular Attenuation Measured at Routine Body #CT

http://onlinelibrary.wiley.com/doi/10.1002/jbmr.3383/abstract

The median post-CT follow-up interval was 5.8 years (interquartile range 2.1–11.0 years). Univariate analysis showed that L1 attenuation values ≤90 Hounsfield units (HU) are significantly associated with decreased fracture-free survival (p < 0.001 by log-rank test). After adjusting for age, sex, prior fracture, glucocorticoid use, bisphosphonate use, chronic kidney disease, tobacco use, ethanol abuse, cancer history, and rheumatoid arthritis history, multivariate analysis demonstrated a persistent modest effect of L1 attenuation on fracture-free survival (hazard ratio HR = 0.63 per 10-unit increase; 95% confidence interval CI 0.47–0.85). The model concordance index was 0.700. Ten-year probabilities for major osteoporosis-related fractures straddled the treatment threshold for most subcohorts over the observed L1 HU range. In conclusion, for patients undergoing body CT scanning for any indication, L1 vertebral trabecular attenuation is a simple measure that, when ≤90 HU, identifies patients with a significant decrease in fracture-free survival

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Incident #fracture is associated with a period of accelerated loss of hip #BMD: the Study of Osteoporotic Fractures

https://link.springer.com/article/10.1007%2Fs00198-018-4606-6


Women with incident upper body fracture or incident lower body fracture exhibited reductions in total hip BMD of 0.89 and 0.77% per year, respectively, while women who did not fracture exhibited reductions in total hip BMD of 0.66% per year during the 4-year period. Accelerated loss of hip BMD was isolated to the 2-year time interval that included the fracture. Loss of total hip BMD was not affected by the number of days from fracture to follow up DXA.

Conclusions
Systemic bone loss following fracture may increase the risk of future fractures at all skeletal sites. There is a need for improved understanding of mechanisms leading to apparent accelerated bone loss following a fracture in order to reduce subsequent fracture risk.

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The associations of subclinical #atherosclerotic cardiovascular disease with hip #fracture risk and bone mineral density in elderly adults

https://link.springer.com/article/10.1007%2Fs00198-018-4611-9

There were 494 hip fractures during follow-up. Among persons without clinical CVD, an average standard-deviation increase in a composite score of maximal common and internal carotid artery intimal medial thickness (cIMT) was associated with increased risk of hip fracture (HR 1.18 [1.04, 1.35), even though cIMT was positively associated with BMD. Neither aortic wall thickness nor ABI were associated with hip fracture risk or BMD. Among participants with clinical CVD, cIMT and aortic wall thickness, but not ABI, were associated with increased hip fracture risk.

Conclusion
Subclinical cIMT is associated with an increased risk of hip fractures despite being associated with increased BMD. This finding suggests that vascular health, even in its early stages, is linked to bone health, by pathways other than BMD

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Association Between #Antidepressant Drug Use and Hip #Fracture in Older People Before and After Treatment Initiation

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2719274

Of the 408 144 people in the register who were included in the study, 257 486 (63.1%) were women, with a mean (SD) age of 80.1 (7.2) years. Antidepressant users sustained more than twice as many hip fractures than did nonusers in the year before and year after the initiation of therapy (2.8% vs 1.1% and 3.5% vs 1.3%, respectively, per actual incidence figures). In adjusted analyses, the odds ratios were highest for the associations between antidepressant use and hip fracture 16 to 30 days before the prescription was filled (odds ratio, 5.76; 95% CI, 4.73-7.01). In all separate analyses of age groups, of men and women, and of individual antidepressants, the highest odds ratios were seen 16 to 30 days before initiation of treatment, and no clear dose-response relationship was seen.

Conclusions and Relevance The present study found an association between antidepressant drug use and hip fracture before and after the initiation of therapy. This finding raises questions about the association that should be further investigated in treatment studies.

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#Fracture Risk After Roux-en-Y Gastric Bypass vs Adjustable #Gastric Banding Among Medicare Beneficiaries

https://jamanetwork.com/journals/jamasurgery/article-abstract/2733040

Roux-en-Y gastric bypass (RYGB) is associated with significant bone loss and may increase fracture risk, whereas substantial bone loss and increased fracture risk have not been reported after adjustable gastric banding (AGB). Previous studies have had little representation of patients aged 65 years or older, and it is currently unknown how age modifies fracture risk.

..Site-specific analyses demonstrated an increased fracture risk at the hip (HR, 2.81; 95% CI, 1.82-4.49), wrist (HR, 1.70; 95% CI, 1.33-2.14), and pelvis (HR, 1.48; 95% CI, 1.08-2.07) among RYGB recipients. No significant interactions of fracture risk with age, sex, diabetes status, or race were found. In particular, adults 65 years and older showed similar patterns of fracture risk to younger adults. Sensitivity analyses using propensity score matching showed similar results (nonvertebral fracture: HR 1.75; 95% CI, 1.22-2.52).

Conclusions and Relevance This study of a large, US population–based cohort including a substantial population of older adults found a 73% increased risk of nonvertebral fracture after RYGB compared with AGB, including increased risk of hip, wrist, and pelvis fractures. Fracture risk was consistently increased among RYGB patients vs AGB across different subgroups, and to a similar degree among older and younger adults. Increased fracture risk appears to be an important unintended consequence of RYGB.

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Association of High Intakes of Vitamins #B6 and #B12 From Food and Supplements With Risk of Hip #Fracture Among Postmenopausal Women in the Nurses’ Health Study

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2733176

..Median (interquartile range) cumulative average intakes of total vitamins B6 and B12 were 3.6 (4.8) mg/d and 12.1 (11.7) μg/d, respectively. Both vitamin B6 (RR, 1.29; 95% CI, 1.04-1.59 for an intake of ≥35 vs <2 mg/d; P = .06 for linear trend) and vitamin B12 (RR, 1.25; 95% CI, 0.98-1.58 for an intake of ≥30 vs <5 μg/d; P = .02 for linear trend) were associated with increased fracture risk. Risk was highest in women with a combined high intake of both vitamins (B6 ≥35 mg/d and B12 ≥20 μg/d), exhibiting an almost 50% increased risk of hip fracture (RR, 1.47; 95% CI, 1.15-1.89) compared with women with a low intake of both vitamins (B6 <2 mg/d and B12 <10 μg/d).

Conclusions and Relevance In this cohort study, a combined high intake of vitamins B6 and B12 was associated with an increased risk of hip fracture. The intakes were far higher than the recommended dietary allowances. These findings add to previous studies suggesting that vitamin supplements should be used cautiously because adverse effects can occur.

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Comparison of #fracture risk using different supplemental doses of #vitamin D, #calcium or their combination: a network meta-analysis of randomised controlled trials

Inconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people

A total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures.

Conclusions The use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully.

https://bmjopen.bmj.com/content/9/10/e024595

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#Atopic eczema and #fracture risk in adults: A population-based cohort study

Those with eczema had increased risk of hip (HR, 1.10; 99% CI, 1.06-1.14), pelvic (HR, 1.10; 99% CI, 1.02-1.19), spinal (HR, 1.18; 99% CI, 1.10-1.27), and wrist (HR, 1.07; 99% CI, 1.03,-1.11) fractures. We found no evidence of increased proximal humeral (HR, 1.06; 99% CI, 0.97-1.15) fracture risk. Fracture risk increased with increasing eczema severity, with the strongest associations in people with severe eczema (compared with those without) for spinal (HR, 2.09; 99% CI, 1.66-2.65), pelvic (HR, 1.66; 99% CI, 1.26-2.20), and hip (HR, 1.50; 99% CI, 1.30-1.74) fractures. Associations persisted after oral glucocorticoid adjustment.

Conclusions
People with atopic eczema have increased fracture risk, particularly major osteoporotic fractures.

https://www.jacionline.org/article/S0091-6749(19)31251-5/fulltext

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#Aspirin and #fracture risk: a systematic review and exploratory meta-analysis of observational studies

This review provides insights into the potential for aspirin to preserve bone mineral density (BMD) and reduce fracture risk, building knowledge of the risk-benefit profile of aspirin.

..Aspirin use was associated with a 17% lower odds for any fracture (OR 0.83, 95% CI 0.70 to 0.99; I2=71%; six studies; n=511 390). Aspirin was associated with a higher total hip BMD for women (SMD 0.03, 95% CI −0.02 to 0.07; I2=0%; three studies; n=9686) and men (SMD 0.06, 95% CI −0.02 to 0.13, I2=0%; two studies; n=4137) although these associations were not significant. Similar results were observed for lumbar spine BMD in women (SMD 0.03, 95% CI −0.03 to 0.09; I2=34%; four studies; n=11 330) and men (SMD 0.08; 95% CI −0.01 to 0.18; one study; n=432).

Conclusions While the benefits of reduced fracture risk and higher BMD from aspirin use may be modest for individuals, if confirmed in prospective controlled trials, they may confer a large population benefit given the common use of aspirin in older people.

https://bit.ly/2VnYufh

Atypical Femur #Fracture Risk versus Fragility Fracture Prevention with #Bisphosphonates
https://2medical.news/2020/08/26/atypical-femur-fracture-risk-versus-fragility-fracture-prevention-with-bisphosphonates/

Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femur fractures have contributed to substantially decreased bisphosphonate use, and the incidence of hip fractures may be increasing. Important uncertainties remain regarding the association between atypical femur fractures and bisphosphonates and other risk factors.. ..Among 196,129 women, 277 atypical femur fractures occurred. After multivariable adjustment, the risk of atypical fracture increased with …

#Height Loss in Old Age and #Fracture Risk Among Men in Late Life: A Prospective Cohort Study
https://2medical.news/2021/03/02/height-loss-in-old-age-and-fracture-risk-among-men-in-late-life-a-prospective-cohort-study/

To assess the association of height loss in old age with subsequent risk of hip and any clinical fracture in men late in life while accounting for the competing risk of mortality, we used data from 3,491 community‐dwelling men (mean age 79.2 years). Height loss between baseline and follow‐up (mean 7.0 years between examinations) was categorized as <1 cm (referent group), ≥1 to <2 cm, …