Juvenile Paget disease: life-long features of a mildly affected young woman

Unusually mild Juvenile Paget Disease (JPD) was extensively investigated in a mentally retarded 21-year-old white woman. Progressive bowing deformitity of her lower limbs began at age 1 1/2 years. Nontraumatic fractures of both femora and both tibias occurred between ages 9 and 14 years. During adulthood, cortical thickening, osteosclerosis, and bowing affected these bones. Serum alkaline phosphatase (ALP) activity was persistently elevated. We found her serum osteocalcin and urinary hydroxyproline and pyridinoline/deoxypyridinoline to also be increased. The iliac crest histology, at ages 14 and 21 years, showed wide cortices and enhanced skeletal remodeling yet the bone was exclusively lamellar. Features of classic Paget Bone Disease (PBD)--such as hypermultinucleated osteoclasts, peritrabecular fibrosis, and mosaic or woven bone--were absent. Electron microscopy revealed no cytoplasmic or nuclear inclusions. Her dermal fibroblasts in culture synthesized unremarkable levels of ALP with proper membrane topography and lipid anchoring; ALP released into the medium also appeared normal. Six months of synthetic human calcitonin therapy daily appeared to reduce here lower limb pain and warmth, but the radiographs, biochemical parameters of skeletal turnover, and bone scintigraphy were unaltered. Lamellar bone has been reported in JPD but accompanied by excessive amounts of woven bone. Our patient reveals that lamellar bone without features of PBD can characterize the skeletal histopathology of the especially rare case of mild JPD.