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Fibrogenesis imperfecta ossium: ineffectiveness of melphalan
M Lafage-Proust1, T Schaeverbeke, J Dehais
1Laboratoire de Biologie du Tissu Osseux, Faculté de Médecine, 15 rue A. Paré, 42023 Saint-Etienne, Cedex 2, France.
Abstract:
Fibrogenesis imperfecta ossium (FIO) is an extremely rare, acquired, metabolic bone disease related to a collagen defect in bone matrix inducing spontaneous fractures. Among the 17 cases of FIO reported to date, four patients exhibited a monoclonal gammopathy (MCG) and one, treated with melphalan, was the first patient to present clinical and histological remission of the bone and plasma cell manifestations. We report the case of a 56-year-old woman who suffered spontaneous fractures of both patellae and olecranons. Skeletal X-rays showed generalized coarse, ill-defined trabeculae. The following biological parameters were abnormal: ESR: 50 mm/hour, alkaline phosphatase (AP) 256 IU/liter [normal (N): 40-110], serum IgG kappa light chain 11 g/liter, bone marrow aspirate 9% atypical plasma cells. Iliac crest biopsy showed the features of FIO including evidence of osteomalacia and nonbirefringent osteoid seams under polarized light. Eroded surfaces were increased, and trabecular bone volume was decreased. Melphalan (4 mg/day) was given in 1988 and was interrupted 1 year later because of leucopenia. Clinical status worsened. A second bone biopsy in 1989 showed identical features of FIO. In November 1990, an X-ray film showed several fractures, and coarser trabeculae. The patient died in December 1991. Regarding the prevalence of MCG and FIO, their association is unlikely accidental. The collagen defect might be related to a plasma cell-induced osteoblast impairment.
Insights
Fibrogenesis imperfecta ossium (FIO), a rare bone disorder, may be linked to monoclonal gammopathy (MCG). This association suggests plasma cells could impair bone collagen formation, leading to fractures.
Area of Science:
- Bone biology
- Metabolic bone diseases
- Connective tissue disorders
Background:
- Fibrogenesis imperfecta ossium (FIO) is an extremely rare metabolic bone disease characterized by collagen defects and spontaneous fractures.
- Monoclonal gammopathy (MCG) has been observed in a subset of FIO patients, suggesting a potential link.
Observation:
- A 56-year-old woman presented with spontaneous fractures, abnormal bone histology consistent with FIO, and monoclonal IgG kappa light chain.
- Skeletal X-rays revealed coarse, ill-defined trabeculae, and bone biopsy showed osteomalacia and increased eroded surfaces.
Findings:
- Despite treatment with melphalan, the patient's condition worsened, with persistent FIO features and new fractures.
- The co-occurrence of FIO and MCG in this case, and previously reported cases, suggests their association is unlikely coincidental.
Implications:
- The findings suggest a potential role for plasma cell dyscrasia in FIO pathogenesis.
- This association may indicate that plasma cell-derived factors could impair osteoblast function and bone matrix collagen synthesis.