Risk of femoral shaft and subtrochanteric fractures among users of bisphosphonates and raloxifene

Vestergaard, Peter; Schwartz, Frederik; Rejnmark, Lars; Mosekilde, Leif

doi:10.1007/s00198-010-1512-y

Cited by 58 publications

(39 citation statements)

References 21 publications

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“…Consistent with these results, data from another Danish cohort suggest that the risk of subtrochanteric/ diaphyseal fractures and all fractures is present before BP initiation. (96) In summary, the Danish data indicate no greater risk for a subtrochanteric or diaphyseal femoral fracture in alendronatetreated patients than for an osteoporosis-related fracture of any part of the femur (including the hip). (94,95) Studies of this type provide important broad and contextual data on the epidemiologic characteristics and incidence of subtrochanteric and diaphyseal femoral fractures.…”

Section: Epidemiology Of Subtrochanteric and Femoral Shaft Fracturesmentioning

confidence: 88%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

989

679

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Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. ß

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Section: Epidemiology Of Subtrochanteric and Femoral Shaft Fracturesmentioning

confidence: 88%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

989

679

View full text Add to dashboard Cite

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“…By all accounts, this would only be a small source of uncertainty. Capture of fracture outcomes using national health databases is generally very good for hip fractures, (25,38) but vertebral fractures are regularly missed by healthcare providers. The health databases do not provide information on height, weight, or lifestyle habits-hence we are unable to determine whether the added fracture risk could be due entirely to loss of bone mass and structure or whether low body weight, muscle weakness, or falls could explain part of the risk increase.…”

Section: Fig 2 Women Cumulative Duration Of Low Tsh (Hyperthyroid mentioning

confidence: 99%

The Excess Risk of Major Osteoporotic Fractures in Hypothyroidism Is Driven by Cumulative Hyperthyroid as Opposed to Hypothyroid Time: An Observational Register-Based Time-Resolved Cohort Analysis

Abrahamsen

Jørgensen

Laulund

et al. 2014

Journal of Bone and Mineral Research

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The long-term relationship between hypothyroidism and fracture risk is challenging to dissect because of the modifying influence of subsequent thyroxine replacement with the potential for excessive replacement doses. We studied changes in serum thyrotropin concentration (TSH) over time and association with fracture risk in real-world patients presenting with elevated TSH. All TSH determinations were done in the same laboratory, which served all hospitals and general practices. The study population consisted of all adults with a first measurement of TSH >4.0 mIU/L (n ¼ 8414) or normal TSH (n ¼ 222,138; comparator). We used a Cox proportional hazards analysis incorporating additional time-dependent covariates to represent initiation of thyroxine replacement and cumulative number of periods with high versus low TSH after index date with a mean follow-up of 7.2 years. Elevated baseline TSH was not associated with an increased risk of hip fracture (HR 0.90; 95% CI, 0.80 to 1.02) or major osteoporotic fractures (HR 0.97; 95% CI, 0.90 to 1.05), nor was subsequent thyroxine prescription predictive of increased risk of fractures. The number of subsequent 6-month periods with low TSH-suggesting excessive thyroxine dosing-was significantly associated with increased risk of both hip fracture (HR 1.09; 95% CI, 1.04 to 1.15) and major osteoporotic fracture (HR 1.10; 95% CI, 1.06 to 1.14). When gender-and agestratified analyses for major osteoporotic fractures were undertaken, hyperthyroid time was identified as a predictor of fracture risk in postmenopausal women whereas hypothyroid time predicted increased fracture risk in men below age 75 years. In conclusion, among patients who present with an elevated TSH, the long-term risk of hip and other osteoporotic fractures is strongly related to the cumulative duration of periods with low TSH-likely from excessive replacement. An independent effect of elevated TSH could only be observed in young and middle-aged men, suggesting gender-discrepant consequences on risk.

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“…The same can be said for some unusual subtrochanteric femoral fractures, mostly found in women on alendronate. Here again there are extensive reviews of the subject [Rizzoli et al 2011;Shane et al 2010], and while such fractures are of concern, there is good evidence [Vestergaard et al 2011] that bisphosphonates prevent many more typical fractures than they cause atypical fractures. For both of these potential side effects, much more work is needed to determine whether there really is cause and effect and, if so, to determine whether patients at the greatest risk for the side effects can be identified.…”

Section: Therapeutic Advances In Musculoskeletal Disease 3 (4)mentioning

confidence: 99%

Osteoporosis in Men: Insights for the Clinician

Adler¹

2011

Therapeutic Advances in Musculoskeletal

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Osteoporosis has finally been recognized as an important disorder in men. Men have osteoporotic fractures about 10 years later in life than women. Owing to increasing life expectancy, more fractures are predicted. Important risk factors for men include advancing age, smoking or chronic obstructive pulmonary disease, glucocorticoid therapy, and androgen deprivation therapy for prostate cancer. Other groups at risk for osteoporosis include those with alcohol abuse, men on enzyme-inducing antiseizure drugs, and those with malabsorption or history of surgery for peptic ulcer disease. History and physical examination will likely reveal secondary causes of osteoporosis. Some, but not all organizations, recommend screening for osteoporosis in men older than age 70. In the USA, The Department of Veterans Affairs recommends case finding rather than screening. Evaluation starts with bone mineral density testing by dual energy X-ray absorptiometry of the spine, hip, and in some cases forearm. A few laboratory tests can be helpful, including measurement of 25-hydroxyvitamin D. Most studies of osteoporosis therapy in men are small; but alendronate, risedronate, zoledronic acid, and teriparatide are FDA-approved to increase bone density in men with osteoporosis. A new potent antiresorptive agent, denosumab, increased bone density dramatically in men on androgen deprivation therapy and is approved for this indication in Europe. Recognition, diagnosis, and treatment of osteoporosis in men should lead to fewer fractures and probably fewer deaths.

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Risk of femoral shaft and subtrochanteric fractures among users of bisphosphonates and raloxifene

Cited by 58 publications

References 21 publications

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

The Excess Risk of Major Osteoporotic Fractures in Hypothyroidism Is Driven by Cumulative Hyperthyroid as Opposed to Hypothyroid Time: An Observational Register-Based Time-Resolved Cohort Analysis

Osteoporosis in Men: Insights for the Clinician

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