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Response to Parathyroid Hormone and 1,25-Dihydroxyvitamin D₃ of Bone-Derived Cells Isolated from Normal Children and Children with Abnormalities in Skeletal Development

INSERM U.234 Höpital Edouard Herriot Lyon, France
INSERM U.30 and CNRS UA.583, Hôpital des Enfants-Malades Paris, France

Address correspondence and requests for reprints to: C. Silve, INSERM U.30 and CNRS UA.583, Hopital des Enfants-Malades, Tour Technique 6ème Etage, 149, rue de Sèvres, 75743 Paris Cedex 15, France.

In order to evaluate the role of intrinsic defects in osteoblast function in the pathogenesis of diseases of skeletal development, we developed techniques which permit the evaluation of the metabolic properties of bone-derived cells in vitro. Cells from control children demonstrated a variety of properties classically attributed to osteoblasts (presence of alkaline phosphatase positive cells and synthesis of bone gla protein) and responded to PTH (cAMP production) and to 1,25-dihydroxyvitamin D₃ (1,25(OH₂D₃) ([³H]25-hydroxyvitamin D₃ conversion into [³H]24,25-dihydroxyvitamin D₃ and bone gla protein secretion). Using these techniques we evaluated the function of cultured bone cells from patients with three rare diseases of skeletal development. Cells from a patient with rickets resistant to 1,25(OH)₂D₃ were resistant to 1,25(OH)₂D₃ but responded normally to PTH. Cells from a patient with acroosteolysis with osteoporosis responded normally to PTH and 1,25(OH)₂D₃. Cells from a patient with hyperphosphatasia with osteoectasia responded normally to 1,25(OH)₂D₃ but did not respond to PTH. The results demonstrate that bone cell cultures can provide information about the role of osteoblast dysfunction in such diseases.

Received August 12, 1985.

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