Differences in bone histomorphometry between white postmenopausal women with and without atypical femoral fracture after long-term bisphosphonate therapy.

Bone histomorphometric endpoints in transilial biopsies may be associated with increased risk of atypical femoral fracture (AFF) in patients with osteoporosis who take antiresorptives, including bisphosphonates (BP). One way to test this hypothesis is to evaluate bone histomorphometric endpoints in age-, gender-, and treatment time matched patients who either had AFF or did not have AFF. In this study, we performed trans-iliac bone biopsies in 52 white postmenopausal women with (n = 20) and without (n = 32) AFFs, all of whom had been treated for osteoporosis continuously with alendronate for 4 to 17 years. Despite the matched range of treatment duration (4-17 yrs), AFF patients received alendronate for significantly longer (10.7 yrs) than non-AFF patients (8.0 yrs) (p = 0.014). Bone histomorphometric endpoints reflecting microstructure and turnover were assessed in cancellous, intracortical and endocortical envelopes from transilial biopsy specimens obtained from BP-treated patients 3-6 months after AFF and from non-AFF patients with similar age-, gender-, and range of BP treatment duration. However, in both cancellous and intracortical envelopes, AFF patients had significantly lower wall thickness (W.Th) and higher osteoclast surface (Oc.S/BS) than non-AFF patients. In addition, AFF patients had significantly higher eroded surface (ES/BS) only in the intracortical envelope. None of the dynamic variables related to bone formation and turnover differed significantly between the groups. In conclusion, in the ilium of BP-treated patients with osteoporosis, AFF patients have lower thickness of superficial bone (lower W.Th) of the cancellous and cortical envelopes than non-AFF patients. AFF and non-AFF patients have similar bone turnover rate in the ilium. Furthermore, in this population, as in previous work, AFF is more likely to occur in BP-treated patients with longer treatment duration.