Responses to Treatment With Teriparatide in Patients With Atypical Femur Fractures Previously Treated With Bisphosphonates

Abstract

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. We 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. We studied 14 patients. Baseline BMD, BTM, and TBS varied widely. On initial bone biopsies, 12 of 14 patients showed tetracycline labels, but mineralizing surface/bone surface was below published normal values in all but 2. Lumbar spine BMD increased significantly at month 24 (6.1% ± 4.3%, p < 0.05 versus baseline), whereas total hip BMD and TBS did not change significantly. Changes in BTM occurred as reported previously for patients without AFF treated with teriparatide after prior bisphosphonate treatment. At month 24, fractures were healed in 6 patients, showed partial healing in 3, were unchanged in 2, and showed nonunion in 1. In a patient with two fractures, the fracture that occurred before teriparatide treatment was reported as healed, but the fracture that occurred while on treatment showed only partial healing. Bisphosphonate-treated patients who sustain AFF show heterogeneity of bone turnover. 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. © 2017 American Society for Bone and Mineral Research.

Teriparatide for treatment of patients with bisphosphonate-associated atypical fracture of the femur

“…In a recent study by Watts et al [20] whose results were consistent with ours, 14 patients with AFF previously treated with bisphosphonates were followed on teriparatide treatment for 24 months. These patients had fractured 52–410 days prior to beginning teriparatide therapy, and five were incomplete fractures.…”

“…Although previous observational studies have often been retrospective, and some have been based on database classification of an AFF, our study was designed to include AFFs that satisfied the majority of the ASBMR classification criteria. In the investigation by Watts et al, they reported that only three of 14 patients demonstrated healing at 12 months, but the definitions of healing were not provided [20]. However, at 24 months, seven of 14 had healed.…”

Osteoporosis, bone mineral density and CKD–MBD: treatment considerations

“…A gradual decrease in bone mass has been noted after discontinuation of teriparatide therapy; however, immediate follow-up therapy (consolidation therapy) with a bisphosphonate has been shown to preserve the benefits [92]. Interestingly, variable positive responses (increased bone turnover markers and BMD) to treatment with teriparatide have been reported in patients with atypical femur fractures previously treated with bisphosphonates, but teriparatide should not be relied on to aid in healing of the atypical femur fractures since no consistent effect on fracture healing was observed [93].…”

MANAGEMENT OF ENDOCRINE DISEASE: Atypical femoral fractures: risks and benefits of long-term treatment of osteoporosis with anti-resorptive therapy

“…Since that time, there have been some investigations of bone turnover by histomorphometry and serum markers. In a very recent study [11], patients meeting the updated ASBMR definition of AFF were recruited for an open label study of teriparatide treatment. At baseline, only 1 of 14 subjects had a serum C-telopeptide (CTX) below the reference range, although 5 had levels of bone specific alkaline phosphatase below the normal range.…”

“…Thus, there is obvious heterogeneity in bone histomorphometry, but we cannot conclude that severe suppression of bone turnover is a constant finding in patients with AFF. In another recent study [11] bone was obtained adjacent to the fracture site in women undergoing surgical repair. Using nanoindentation and vibrational spectroscopy, the authors showed that bone was harder and more mineralized in women with atypical fractures after [14], was enough to prevent healing of the crack.…”