THU435 Atypical Femur Fractures In Antiresorptive- Therapy-naïve Patient Underscores Knowledge Gaps

Disclosure: T.L. Cater: None. M. Styner: None. Atypical femur fractures (AFF), so-named due to an unusual diaphyseal location, have been linked to antiresorptives (AR), though this remains unclear. AFF case reports are vital due to a lack of certainty about pathogenic mediators and management. Case: A 52-yr-old-female presented with symptomatic T6/T7/T8 compression sustained while raking acorns. Ten years prior, bilateral knee/thigh pain developed; X-ray showed mild arthritis; bone scan noted slight activity in lateral femoral cortices with later X-ray read as negative for fracture; DEXA indicated lowest T of −1.5 in the spine. She was managed with PT and bracing. Medical history included hip dysplasia s/p casting, endometriosis, infertility, hypothyroidism, and 2 full-term NSVD in her late 30s. She worked as an administrator before becoming a stay-at-home mom and denied alcohol or tobacco use. Family history was notable for hip fracture (mother) and hypermobility termed as Ehlers-Danlos (son). After thoracic healing, at 53, she was referred to endocrinology; exam showed Ht 69 in (175 cm), Wt 185 lb (83 kg), normal dentition, mild thoracic kyphosis without tenderness. Labs indicated normal Ca, Mg, PO4, Creat, 25(OH)D, Alk Phos, and SPEP. She was current on cancer screening including mammograms. She declined osteoporosis therapy, wishing to work on lifestyle, yet, when she returned to our clinic at 55, after new compression (T11/T12/L1), she was amenable to begin abaloparatide. Despite the anabolic, new L2/L3 fracture arose and thigh pain advanced. Genetic Invitae OI/bone fragility panel was negative for causal variants in 46 genes. DEXA showed 20% improved spine BMD: 5-15% in other sites. After 2 years of abaloparatide and 4 months after one-time dose of denosumab, a new L4 deformity arose, and thigh pain remained. She reported legs were giving way under her, prompting X-rays, which were concerning for bilateral AFF (confirmed with bone scan, MRI). In lieu of a 2(nd) dose of denosumab, romosozumab was started and she was promptly scheduled for prophylactic, orthopedic femoral nailing. Conclusions: This bisphosphonate-naïve-female began experiencing symptoms of AFF >5 years prior to presentation, concomitant with spine fragility. Skeletal deterioration occurred in absence of, as well as contemporaneous with, osteoporosis therapies, anabolic as well as one dose of AR despite improved BMD via DEXA. Her personal history of hip dysplasia might supply clues about geometry that favors AFF as her family history. Notably, long-standing discomfort in the thighs persisted and progressed during anabolic therapy. More research is needed to understand AFF pathogenesis, and this might also shed light on other severe forms of early bone fragility, as demonstrated herein. Our case also highlights a multi-year, sub-clinical period in which fragility progresses until a clinical diagnosis is reached, as well as the clinical conundrum of AFF management. Presentation: Thursday, June 15, 2023