Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Atypical femur fracture following denosumab therapy in bisphosphonate naïve postmenopausal woman (#401)

Tegan Millington 1 , Sonia Stanton 1
  1. The Canberra Hospital Endocrinology Department, ACT Health, Canberra, ACT, Australia

A 63-year-old post-menopausal woman presented with an atypical femoral fracture (AFF) in September 2019. She had been on denosumab therapy (60mg every six months) for seven years without prior bisphosphonate use. Her medical history included several minimal trauma fractures, including an atraumatic left ankle fracture and a right tibial fracture. A bone mineral density (BMD) scan in 2013 showed a T-score of -2.9 at the femoral neck, leading to denosumab treatment for osteoporosis.

The fracture occurred from a standing height without any prodromal pain. Imaging confirmed an oblique transverse, minimally comminuted fracture of the left femur, consistent with an AFF. Surgical intervention with an intramedullary nail was performed. Imaging of the contralateral femur showed cortical thickening without signs of impending fracture.

Atypical femoral fractures are rare complications of long-term bisphosphonate use (1). Reports of AFFs in denosumab-treated patients, particularly those without prior bisphosphonate exposure, are less common, with only five documented cases in the literature (2). However, clinical experience suggests the incidence of AFFs may be underestimated.

The FREEDOM study, a randomized placebo-controlled trial involving 7,868 post-menopausal women, found no significant association between denosumab and AFFs over three years (3), although two cases were reported during extended follow-up (4,5). Due to the patient's fracture history and potential AFF risk on the contralateral side, continued osteoporosis therapy was necessary. However, bisphosphonates were avoided due to their associated AFF risk.

After a repeat BMD scan showed positive T-scores, denosumab therapy was resumed at a reduced dose (30mg every six months) following a 12-month hiatus. Bone turnover markers were normal, and the patient had no further fractures, with the left femur healing successfully.

This case highlights the rare occurrence of AFF in long-term denosumab patients without prior bisphosphonate use, underscoring the need for research into individualized dosing strategies for managing complex fracture cases.66b5d93611857-Fig+1.PNG

  1. 1. Shane E, Burr D, Abrahamsen B, Adler RA et al (2014) Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 29(1):1–23.
  2. 2. Kumar S, Chang R, Reyes M, Diamond T. Atypical femoral fracture in a bisphosphonate-naïve patient on denosumab for osteoporosis. Arch Osteoporos. 2022 Oct 1;17(1):131.
  3. 3. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765
  4. 4. Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, Czerwiński E, Fahrleitner-Pammer A, Kendler DL, Lippuner K, Reginster JY, Roux C, Malouf J, Bradley MN, Daizadeh NS, Wang A, Dakin P, Pannacciulli N, Dempster DW, Papapoulos S. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017 Jul;5(7):513-523
  5. 5. Bone HG, Chapurlat R, Brandi ML et al (2013) The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab 98(11):4483–4492.