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


BACKGROUND
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.
Division of Pharmacoepidemiology, Harvard Medical School, Boston, MA, USA. dsolomon@partners.org
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D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D016001:Confidence Intervals; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D005599:Fractures, Ununited / Q000139:chemically induced*; D006801:Humans; D006810:Humeral Fractures / Q000139:chemically induced*; D008297:Male; D010024:Osteoporosis / Q000150:complications / Q000188:drug therapy*; D012307:Risk Factors; D013997:Time Factors
D050071:Bone Density Conservation Agents; D004164:Diphosphonates