24Jul 2017
MPubmed

The clinical significance of osteoporosis is in the occurrence of fractures and re-fractures. The main risk factor of sustaining a fracture is a previous one, but a recent fracture is a better fracture risk factor than fracture history. The role of the recency of fracture has been shown for both vertebral and non-vertebral fracture risk. This imminent risk is explained by both bone-related factors (underlying osteoporosis) and fall-related factors (including those related to postfracture care). Such a short-term increased risk has been shown also in patients initiating corticosteroids and in frail osteoporotic subjects with central nervous system (CNS) diseases or drugs targeting CNS, and thus a high risk of falls. Patients with an imminent (i.e. 2 years) risk of fracture or refracture should be identified in priority in order to receive an immediate treatment and a program of fall prevention.

Osteoporos Int. 2017 Jun;28(6):1765-1769. doi: 10.1007/s00198-017-3976-5. Epub 2017 Feb 24. Review.

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Roux C, Briot K.

24Jul 2017
MPubmed

It has been suggested that normalization of bone turnover may improve clinical outcome in Paget’s disease of bone (PDB) by preventing complications such as fractures and the development of osteoarthritis. Here we investigated the long-term effects of a treatment strategy that aimed to normalize bone turnover in PDB with that of symptomatic treatment. The study group comprised 502 subjects who were enrolled into a 3-year extension of the Paget’s Disease: Randomized Trial of Intensive versus Symptomatic Management (PRISM) study. Intensive bisphosphonate therapy was continued in 270 of these subjects with the aim of normalizing bone turnover using zoledronic acid as the treatment of first choice. Symptomatic treatment continued in 232 subjects in whom bisphosphonates were only given for the treatment of bone pain. Intensive treatment was associated with a nonsignificant increase in fracture risk (hazard ratio = 1.90; 95% CI, 0.91 to 3.98; p = 0.087), orthopedic procedures (1.81; 95% CI, 0.71 to 4.61; p = 0.214), and serious adverse events (relative risk 1.28; 95% CI, 0.96 to 1.42). We conclude that long-term intensive bisphosphonate therapy confers no clinical benefit over symptomatic therapy and is associated with a nonsignificant increase in the risk of fractures, orthopedic events, and serious adverse events.

J Bone Miner Res. 2017 Jun;32(6):1165-1173. doi: 10.1002/jbmr.3066. Epub 2017 Feb 8.

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Tan A, Goodman K, Walker A, Hudson J, MacLennan GS, Selby PL, Fraser WD, Ralston SH; PRISM-EZ Trial Group.

24Jul 2017
MPubmed

Randomized clinical trials that evaluated the efficacy of a treatment for osteoporosis or low bone mineral density for adult men and reported fracture outcomes.

Twenty-four articles reporting results for 22 studies (including 4,868 male participants) met strict inclusion criteria. Fixed-effects meta-analyses using the Mantel-Haenszel method demonstrated significantly lower risk of vertebral fractures with alendronate (relative risk (RR) = 0.328, 95% confidence interval (CI) = 0.155-0.692) and risedronate (RR = 0.428, 95% CI = 0.245-0.746) but not with calcitonin (RR = 0.272, 95% CI = 0.046-1.608) or denosumab (RR = 0.256, 95% CI = 0.029-2.238) than in controls. For bisphosphonates as a treatment category, meta-analyses demonstrated significantly lower risk of vertebral fractures (RR = 0.368, 95% CI = 0.252-0.537) and nonvertebral fractures (RR = 0.604, 95% CI = 0.404-0.904) than in controls. The meta-analysis finding that bisphosphonates significantly reduce nonvertebral fracture risk was not robust to sensitivity analysis.

Bisphosphonates reduce the risk of vertebral and possibly nonvertebral fractures for men with osteoporosis. Further studies are needed to evaluate the efficacy of bisphosphonates for reducing nonvertebral fracture risk and the efficacy of nonbisphosphonates for reducing vertebral and nonvertebral fracture risk in men with osteoporosis.

J Am Geriatr Soc. 2017 Mar;65(3):490-495. doi: 10.1111/jgs.14668. Epub 2016 Nov 7. Review.

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Nayak S, Greenspan SL.

24Jul 2017
MPubmed

This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women. This guideline is endorsed by the American Academy of Family Physicians. The ACP Clinical Guidelines Committee based these recommendations on a systematic review of randomized controlled trials; systematic reviews; large observational studies (for adverse events); and case reports (for rare events) that were published between 2 January 2005 and 3 June 2011. The review was updated to July 2016 by using a machine-learning method, and a limited update to October 2016 was done. Clinical outcomes evaluated were fractures and adverse events. This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density, including pharmaceutical prescriptions, calcium, vitamin D, and estrogen. Evidence was graded according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

Ann Intern Med. 2017 Jun 6;166(11):818-839. doi: 10.7326/M15-1361. Epub 2017 May 9.

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Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians.

24Jul 2017
MPubmed

Daily subcutaneous (SC) injections of the investigational drug abaloparatide-SC (80 mcg) for 18 months significantly decrease the risk of vertebral and nonvertebral fracture compared with placebo in postmenopausal women. We examined the efficacy of abaloparatide-SC as a function of baseline fracture risk, assessed using the FRAX tool.

A total of 821 women randomized to placebo and 824 women to abaloparatide-SC, mean age 69 years in both groups, were followed for up to 2 years. At baseline, the 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.3% to 57.5% (mean 13.2%). Treatment with abaloparatide-SC was associated with a 69% (95% confidence interval [CI] 38-85%) decrease in major osteoporotic fracture (MOF) and a 43% (95% CI 9-64%) decrease in any clinical fracture compared with placebo. For all outcomes, hazard ratios tended to decrease (ie, greater efficacy) with increasing fracture probability. Whereas the interaction approached significance for the outcome of any fracture (p = 0.11), there was no statistically significant interaction for any of the fracture outcomes. Similar results were noted when FRAX probability was computed without BMD. Efficacy of abaloparatide-SC to decrease the risk of major osteoporotic fracture or any clinical fracture in postmenopausal women with low BMD and/or prior fracture appears independent of baseline fracture probability.

J Bone Miner Res. 2017 May 5. doi: 10.1002/jbmr.3163. [Epub ahead of print.

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McCloskey EV, Johansson H, Oden A, Harvey NC, Jiang H, Modin S, Fitzpatrick L, Kanis JA.

21Jun 2017
MPubmed

This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly fall into four distinct themes: (1) case finding and management of individuals at high risk of fracture, (2) public awareness of osteoporosis and fragility fractures, (3) reimbursement and health system policy and (4) epidemiology of fracture in the developing world. In the developing world, robust epidemiological estimates of fracture incidence are required to inform policy development. As the aging of the baby boomer generation is upon us, this review provides a comprehensive analysis of how bone health can be improved worldwide for all.

Osteoporos Int. 2017 May;28(5):1507-1529. doi: 10.1007/s00198-016-3894-y.

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Harvey NC, McCloskey EV, Mitchell PJ, Dawson-Hughes B, Pierroz DD, Reginster JY, Rizzoli R, Cooper C, Kanis JA.

21Jun 2017
MPubmed

A case series of six women with postmenopausal osteoporosis who had received continuous denosumab for 7 years and were then given a single infusion of zoledronate (5 mg) is reported. During denosumab treatment, bone mineral density (BMD) in the spine increased 18.5% (P = 0.006), and total hip BMD by 6.9% (P = 0.03). Post-zoledronate BMDs were measured 18-23 months after treatment, and there were significant declines at each site (P spine = 0.043, P hip = 0.005). Spine BMD remained significantly above the pre-denosumab baseline (+9.3%, P = 0.003), but hip BMD was not significantly different from baseline (-2.9%). At the time of post-zoledronate BMD measurements, serum PINP levels were between 39 and 60 μg/L (mean 52 μg/L), suggesting that the zoledronate treatment had not adequately inhibited bone turnover. It is concluded that this regimen of zoledronate administration is not adequate to preserve the BMD gains that result from long-term denosumab treatment.

Calcif Tissue Int. 2017 May 13. doi: 10.1007/s00223-017-0288-x.

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Reid IR, Horne AM, Mihov B, Gamble GD

21Jun 2017
MPubmed

Type 1 and type 2 diabetes are generally accepted to be associated with increased bone fracture risk. However, the pathophysiological mechanisms of diabetic bone disease are poorly understood, and whether the associated increased skeletal fragility is a comorbidity or a complication of diabetes remains under debate. Although there is some indication of a direct deleterious effect of microangiopathy on bone, the evidence is open to question, and whether diabetic osteopathy can be classified as a chronic, microvascular complication of diabetes remains uncertain. Here, we review the current knowledge of potential contributory factors to diabetic bone disease, particularly the association between diabetic microangiopathy and bone mineral density, bone structure, and bone turnover. Additionally, we discuss and propose a pathophysiological model of the effects of diabetic microvascular disease on bone, and examine the progression of bone disease alongside the evolution of diabetes.

Lancet Diabetes Endocrinol. 2017 May 22. pii: S2213-8587(17)30134-1. doi: 10.1016/S2213-8587(17)30134-1.

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Shanbhogue VV, Hansen S, Frost M, Brixen K, Hermann AP

21Jun 2017
MPubmed

If oversuppression of bone turnover explained the association between bisphosphonate use and atypical subtrochanteric femur fractures (AFF), this could be reversed with anabolic treatment such as teriparatide. They conducted a prospective, open-label study in patients previously treated with bisphosphonates who sustained AFF, examining the response to 24-month treatment with teriparatide on bone mineral density (BMD), trabecular bone score (TBS), bone turnover markers (BTM), and fracture healing as well as quantitative histomorphometry. Treatment with teriparatide resulted in increases in BTM and lumbar spine BMD, as has been reported for patients without AFF. There was no significant effect of teriparatide on hip BMD, mineralizing surface to bone surface (MS/BS), or TBS and no consistent effect on fracture healing. In the context of a patient who has experienced an AFF after receiving bisphosphonate treatment, therapy with teriparatide for 24 months would be expected to increase BMD and BTM (and probably reduce the risk of fractures resulting from osteoporosis) but should not be relied on to aid in healing of the AFF.

J Bone Miner Res. 2017 May;32(5):1027-1033. doi: 10.1002/jbmr.3081. Epub 2017 Feb 7.

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Watts NB, Aggers D, McCarthy EF, Savage T, Martinez S, Patterson R, Carrithers E, Miller PD.