Evidence of reduced bone turnover and disturbed mineralization process in a boy with Stickler syndrome.

We describe a tall-statured 14-year-old boy who illustrated the full phenotypic and radiographic features of Stickler syndrome type I. A bone biopsy showed evidence of reduced bone mass and bone turnover, such as reduced BV/TV (-43%), TbTh (-29%), and OS/BS (-48%), Ob.S/BS (-27%), and Oc/BS (-47%) compared to "age-matched" controls. Moreover, there was evidence that the mineralization process was severely disturbed. Quantitative backscattered electron imaging revealed that the bone mineralization density distribution (BMDD) of cancellous (Cn) as well as cortical (Ct) bone was shifted toward lower mineralization compared to a young control reference cohort. BMDD parameters of mean degree of mineralization, Cn Ca (-9.8%) and Ct Ca (-18.0%), were dramatically decreased. To the best of our knowledge this is the first clinical report describing bone biopsy findings in a boy with Stickler syndrome. Such a severe undermineralization of bone matrix might essentially contribute to the compromised mechanical competence of the skeleton found in this patient.

Effects of tumor-induced osteomalacia on the bone mineralization process.

Fibroblast growth factor 23 (FGF23) overexpression has been identified as a causative factor for tumor-induced osteomalacia (TIO) characterized by hypophosphatemia due to increased renal phosphate wasting, low 1,25(OH)(2)D(3) serum levels, and low bone density. The effects of long-lasting disturbed phosphate homeostasis on bone mineralization are still not well understood. We report on a patient with a 12-year history of TIO, treated with 1,25(OH)(2)D(3) and phosphate, who finally developed hyperparathyroidism with gland hyperplasia before the tumor could be localized in the scapula and removed. During surgery a transiliac bone biopsy was obtained. FGF23 expression in the tumor cells was confirmed by in situ hybridization. Serum FGF23 levels as measured by ELISA were found to be extremely elevated before and decreased after removal of the tumor. Bone histology/histomorphometry and measurement of bone mineralization density distribution using quantitative backscattered electron imaging were performed on the bone biopsy. The data showed important surface osteoidosis and a slightly increased osteoblast but markedly decreased osteoclast number. The mineralized bone volume (-11%) and mineralized trabecular thickness (-18%) were low. The mean degree of mineralization of the bone matrix (-7%), the most frequent calcium concentration (-4.1%), and the amounts of fully mineralized bone (-40.3%) were distinctly decreased, while the heterogeneity of mineralization (+44.5%) and the areas of primary mineralization (+131.6%) were dramatically increased. We suggest that the elevated levels of FGF23 and/or low phosphate concentrations disturb the mineralization kinetics in vivo without affecting matrix mineralization of pre-existing bone packets.