Case:
A 63-year-old female presented for evaluation of the pathogenesis of recurrent fractures despite normal/elevated BMD on a background of CKD requiring renal transplant and parathyroidectomy; breast malignancy treated with multimodal therapy; multiple myeloma with autologous stem cell transplant (ASCT); T2DM and ischaemic heart disease. There is a personal and family history of childhood dental issues but no childhood fractures or family history of non-traumatic fractures.
Therapeutic zoledronate (10 doses) was administered over 24-months post ASCT and 8-years later she suffered a left femoral shaft minimal trauma fracture. A subsequent single dose of denosumab was complicated by severe hypocalcaemia. During the next 2-years she suffered rib, scapular, vertebral and peri-prosthetic femur fractures. Investigations 8-months post renal transplant showed normal FBC, tryptase, TFT, LFT, phosphate, corrected calcium, and negative coeliac serology. PTH was 14.7 (N:1.6-6.0), eGFR 29 ml/min/m2, 25-hydroxyvitamin D 96 nmol/L, and bone specific ALP 9.6 (N:5.5-24.6).
DXA demonstrated T-scores of +5.3 ,0.0, and -0.3 at the femoral neck, lumbar spine, and radius, respectively. HR-pQCT showed elevated volumetric BMD at the radius (4.0 SD; 484.4 vs 287.8 mgHA/ccm) and tibia (4.9 SD; 424.0 vs 249.8 mgHA/ccm). Matrix mineral density was 2.4 and 2.0 SD higher in distal radius and tibia respectively, compared to age and sex-matched controls. Whole-body bone scintigraphy demonstrated metabolic activity at un-united fracture sites. Parathyroid sestamibi was negative.
Discussion:
Aetiology of the non-traumatic fractures remains uncertain; the initial fracture may represent an atypical femoral fracture while the other fractures may be due to renal osteodystrophy. Tetracycline labelled bone biopsy and genetic testing for Wnt signalling pathway abnormalities are being considered. Targeted therapy for secondary prevention of fracture is challenging due to the multifactorial nature of her bone fragility, metabolic changes associated with transition from haemodialysis to renal transplant and the history of malignancy and radiotherapy.