Background:

AFF have been associated with use of antiresorptive therapies, however rarer causes include osteopetrosis, Paget’s disease, hypophosphatasia, pycnodysostosis, vitamin D deficiency, and rheumatoid arthritis. These conditions should be considered particularly in antiresorptive naïve individuals.

Case:
A 33-year-old Lebanese woman, five months postpartum, presented with an atraumatic right subtrochanteric femoral fracture after five years of preceding hip pain. She underwent intramedullary nail fixation. She had no dysmorphic features, visual or hearing impairment, and was of normal height. Her parents were first cousins.

Notably, she has a 54-year-old female cousin also with consanguineous parents who was managed for presumed Paget’s disease with three zoledronic acid infusions. She had developed a left atypical femoral fracture five-years after her last zoledronic acid infusion and had an impending right AFF which was managed with a prophylactic intramedullary nail.  Of note, she has a persistently elevated CK level, bilateral optic neuropathy and a son with paraplegia. These features raised the suspicion of an alternative diagnosis.

Investigations demonstrated normocytic anaemia, vitamin D deficiency, hypocalcaemia with secondary hyperparathyroidism, and markedly elevated bone turnover markers. Imaging revealed diffuse osteosclerosis, cortical thickening, trabecular coarsening, a rugger-jersey spine, and markedly elevated bone mineral density (Lumbar spine Z score +5.2, Femoral neck Z-score +8.3). Bone scintigraphy demonstrated widespread symmetrical osteoblastic activity, favouring a metabolic bone disorder rather than Paget's disease. Bone biopsy showed lamellar and woven bone without histological features of Paget's disease. A presumptive diagnosis of osteopetrosis was made, with genetic testing for hereditary osteosclerotic disorders currently pending.

Conclusion:
AFF in an antiresorptive-naïve patient should prompt investigation for an underlying metabolic bone disorder. Consanguinity, family history and characteristic imaging supported a hereditary osteosclerotic disorder. Accurate diagnosis is essential, as osteopetrosis requires supportive multidisciplinary management and genetic counselling, whereas Paget's disease is commonly treated with anti-resorptive therapy.