Multiple fractures in a young woman with normal bone mineral density: Insights from bone microarchitectural assessment.

Introduction: Fracture prevention in young adults with chronic disease and glucocorticoid (GC) exposure is complex and limited by insufficient data. Current guidelines(1) recommend monitoring of bone mineral density (BMD) with dual x-ray absorptiometry (DXA); oral bisphosphonates are recommended over anabolic therapy for those at moderate-high fracture risk.Clinical Case: A 47-year-old woman with a 30-year history of severe rheumatoid arthritis presented for review of osteoporosis management. She had a 20-year fracture history including vertebral, metatarsal and periprosthetic fractures of the left ulna and a more recent non-healing left patella and tibia-fibula fracture. Risk factors for fracture included over 20 years of GC exposure, premature ovarian insufficiency (POI) secondary to cyclophosphamide and pancreatitis secondary to sulfasalazine. She had received oral bisphosphonates for over five years followed by four doses of zoledronic acid. Two years after her final dose of zoledronic acid, she developed osteonecrosis of the jaw (ONJ) after a dental extraction.The patient had normal vitamin D (25-OH vitamin D 102nmol/L; 50-250), creatinine 63umol/L (45 - 85) and corrected calcium 2.44mmol/L (2.15-2.55) levels. Bone turnover markers were unremarkable: CTx 220ng/L (150-800), P1NP 50ug/L (15-70) and ALP 59U/L (20-105). BMD was normal on DXA: L1-L4 (LS) 1.254g/cm2, Z-score -0.3, left neck of femur (NOF) 0.921g/cm2, Z score -1.1 in 2010, increasing to 1.353g/cm2 LS and 1.142g/cm2 NOF by 2018. However, high resolution peripheral quantitative computed tomography (HR-pQCT) identified reduced trabecular and cortical bone volume and a 7.8x6.5x6.7mm area of focal bone loss (Figure 1). While her ONJ improved, trabecular volumetric BMD (Tb.vBMD: 157mgHA/cm3 at radius and 144.3 mgHA/cm3 at tibia) and cortical volumetric BMD (Ct.vBMD; 845.3 mgHA/cm3 radius and 889.5 mgHA/cm3 tibia) did not, (Tbv.BMD 119.0 mgHA/cm3 radius and 114.3 mgHA/cm3 tibia, Ct.vBMD 848.4 mgHA/cm3 radius