Can long-term bisphosphonate use causes low-energy fractures? A case report.

Bisphosphonates are inorganic pyrophosphate analog which accumulate on the bone surface, cause osteoclast apoptosis, and inhibit bone resorption. The nitrogen-containing bisphosphonates continue to be the drug of choice for the treatment of osteoporosis in both men and women. Although histomorphometric studies including bone biopsies have not shown any evidence of microcracks, recent studies have revealed that potent bisphosphonates are responsible for the oversuppression of bone turnover leading to microdamages, reduced bone strength, and increased fracture risk. There are individual cases reporting atypical femoral fractures and severely suppressed bone turnover along with long-term (≥ 5 years) use of biphosphonates. In this study, we report on a 74-year-old woman with a history of continuous alendronate use for nearly 16 years who presented to the emergency department with right proximal humerus and left femur fracture.

Low-energy fractures of the humeral shaft and bisphosphonate use.

Atypical fractures of the femur have been reported to occur in patients on long-term treatment with bisphosphonates; however, causality has not been proven, and it is not known whether similar fractures may occur in other long bones. We addressed this issue by examining the relationship between humeral shaft fractures and bisphosphonate use. We identified all patients aged ≥50 years consecutively admitted to a single center with a new fracture of the humerus. All individual radiographs were examined and fracture site was classified. A case-control study was undertaken in patients with humeral shaft fractures, and controls were sex- and age-matched patients with proximal humeral fractures in a 1:4 ratio. Patients with shaft fractures and radiographic characteristics similar to those of atypical femoral fractures were compared with those with ordinary shaft fractures. The association between "atypical" fractures and bisphosphonate or glucocorticoid use was examined. A total of 198 patients had a low-energy fracture of the humerus; 20 of these patients had a shaft fracture (10%). These 20 patients (cases) were matched with 80 patients with proximal fractures (controls). Bisphosphonates were used by 5% of cases and by 6.3% of controls (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.09-6.85); glucocorticoids were used by 10% of cases and 8.8% of controls (OR, 1.15; 95% CI, 0.23-5.83). There was no difference in cortical thickness between cases and controls and bisphosphonate or glucocorticoid users and nonusers. Four of the 20 patients with shaft fractures had "atypical" radiographic features, with significantly increased cortical thickness, but none of these had ever been treated with bisphosphonates or glucocorticoids. Our results show that low-energy fractures of the humeral shaft with "atypical" radiographic characteristics are infrequent and are not associated with the use of bisphosphonates or glucocorticoids.

The relation between bisphosphonate use and non-union of fractures of the humerus in older adults.

SUMMARY: While nitrogen-containing bisphosphonates have been shown to reduce fracture risk in postmenopausal women and men, their safety in the period after a fracture is unclear. In fully adjusted multivariable regression models, bisphosphonate use in the post-fracture period was associated with an increased probability of non-union [odds ratio (OR) 2.37, 95% confidence interval (CI) 1.13-4.96]. Clinicians might consider waiting for several months before introduction of a bisphosphonate after a fracture. INTRODUCTION: While nitrogen-containing bisphosphonates have been shown to reduce fracture risk in postmenopausal women and men, their safety in the period after a fracture is unclear. We examined the risk of non-union associated with post-fracture bisphosphonate use among a group of older adults who had experienced a humerus fracture. METHODS: We conducted a nested case-control study among subjects who had experienced a humerus fracture. From this cohort, cases of non-union were defined as those with an orthopedic procedure related to non-union 91-365 days after the initial humerus fracture. Bisphosphonate exposure was assessed during the 365 days prior to the non-union among cases or the matched date for controls. Multivariable logistic regression models were examined to calculate the OR and 95% CI for the association of post-fracture bisphosphonate use with non-union. RESULTS: From the cohort of 19,731 patients with humerus fractures, 81 (0.4%) experienced a non-union. Among the 81 cases, 13 (16.0%) were exposed to bisphosphonates post-fracture, while 69 of the 810 controls (8.5%) were exposed in the post-fracture interval. In fully adjusted multivariable regression models, bisphosphonate use in the post-fracture period was associated with an increased odds of non-union (OR 2.37, 95% CI 1.13-4.96). Albeit limited by small sample sizes, the increased risk associated with bisphosphonate use persisted in the subgroup of patients without a history of osteoporosis or prior fractures (OR 1.91, 95% CI 0.75-4.83). CONCLUSIONS: In this study of older adults, non-union after a humerus fracture was rare. Bisphosphonate use after the fracture was associated with an approximate doubling of the risk of non-union.

Inhaled and nasal corticosteroid use and the risk of fracture.

Studies of the risk of fracture associated with inhaled corticosteroids are inconclusive and are limited to short-term effects. We assessed whether long-term use increases this risk. We conducted a case control study nested within a population-based cohort of all Quebec elderly dispensed respiratory medications and followed for at least 4 years during 1988-2001. There were 9,624 new cases of fracture of the hip or upper extremities and 191,622 age-matched control subjects (mean age of 81 years). The rate of any such fracture for current inhaled corticosteroid use was not elevated (rate ratio [RR], 0.97; 95% confidence interval [CI], 0.92-1.03). For upper-extremity fracture, the rate increased by 12% (RR, 1.12; 95% CI, 1.04-1.19) with every 1,000-microg increase in the daily dose of inhaled corticosteroids, but not for hip fracture (RR, 0.97; 95% CI, 0.88-1.07). Among subjects followed for over 8 years, the rate of hip fracture was only elevated with daily doses of more than 2,000 microg of inhaled corticosteroids (RR, 1.61; 95% CI, 1.04-2.50). The rate was not elevated at any dose of nasal corticosteroids. In conclusion, the long-term use of inhaled and nasal corticosteroids at the usual recommended doses is not associated with a risk of fracture in older patients with respiratory disease.

'Mucoid dissolution' of bones and multiple pathologic fractures in a patient with past history of intravenous administration of polyvinylpyrrolidone (PVP). A case report.

Polyvinylpyrrolidone (PVP) has been used in industry as well as in medicine for various purposes, e.g. as a component of hair-sprays, 'retardant' for subcutaneous injections, and given intravenously as a plasma expander. The latter usage results in deposition of PVP in the reticulo-endothelial system and other mesenchymal cells, including osteocytes. A middle aged woman in Taiwan, who for 10 years received repeated intravenous injections of PVP, suffered pathologic fractures of both femora and her right humerus with additional destructive lesions seen radiologically in other bones. Biopsies of the fracture sites showed both intracellular PVP deposits and mucoid changes in the involved cells, a characteristic secondary complication of PVP deposition. This phenomenon, if of sufficient severity, may cause, as in this case, a virtual 'melting down' of osseous tissue with pathological fractures as a consequence.