Bone Mineralization in Polyostotic Fibrous Dysplasia: Histomorphometric Analysis

Abstract

Fibrous dysplasia (FD) of bone can be complicated by renal phosphate wasting. The effect of hypophosphatemia on normal and dysplastic bone of FD patients has not been well characterized. In this study, we compared serum phosphorus (sPi) levels to histomorphometric findings in 27 iliac bone samples from 23 children and adolescents (aged 4.2-16.4 years) with polyostotic FD. The samples were separated into two groups, based on the presence (n ‫؍‬ 10) or absence (n ‫؍‬ 17) of a dysplastic lesion within the specimen. Histomorphometric results were compared with those from 18 age-matched control subjects without metabolic bone disease. In dysplastic lesions, trabeculae were clearly thinner and increased in number. Osteoid indices, osteoblast surface per bone surface, and mineralization lag time were elevated in dysplastic areas, but there was no detectable effect of sPi concentrations on these indices. In nondysplastic bone tissue, low sPi levels were associated with mildly increased osteoid thickness and prolonged mineralization lag time. None of the 13 patients in whom hand X-rays were available at the time of biopsy had radiological signs of rickets. In conclusion, low sPi can cause a mild systemic mineralization defect in FD, but the more severe mineralization defect seen in dysplastic lesions is independent of sPi levels. It is debatable whether the mild systemic mineralization defect warrants treatment with oral phosphorus supplementation if signs of rickets are absent.

Iliac bone histomorphometry in children with newly diagnosed inflammatory bowel disease

“…Osteoid thickness was below 9 μm in all patients, which is the cutoff value above which a mineralization defect is diagnosed in pediatric histomorphometry, as proposed earlier [28]. Osteoid surface and volume as well as bone resorption parameters were low compared to age-specific norms.…”

Outcome of Long-Term Bisphosphonate Therapy in McCune-Albright Syndrome and Polyostotic Fibrous Dysplasia

“…Active metabolites of vitamin D and phosphate supplements were additionally prescribed as required, predominantly in children, prior to start treatment with bisphosphonates, to correct moderate to severe hypophosphatemia associated with FGF‐23–induced renal phosphate wasting. The decision not to treat FGF‐23–induced mild hypophosphatemia in the absence of overt osteomalacia was based on published histomorphometry data in FD (albeit in children and adolescents), suggesting that although low serum phosphate may be associated with a mild systemic mineralization defect in PFD, it was debatable whether this warranted treatment in the absence of signs of rickets, as the more severe mineralization defect observed in dysplastic lesions was independent of serum phosphate levels …”

“…The decision not to treat FGF-23-induced mild hypophosphatemia in the absence of overt osteomalacia was based on published histomorphometry data in FD (albeit in children and adolescents), suggesting that although low serum phosphate may be associated with a mild systemic mineralization defect in PFD, it was debatable whether this warranted treatment in the absence of signs of rickets, as the more severe mineralization defect observed in dysplastic lesions was independent of serum phosphate levels. (30) Clinical and biochemical response to treatment in the form of verbal assessment of pain and biochemical markers of bone turnover and recurrence of FD activity after discontinuation of treatment were evaluated during outpatient clinic visits at start of treatment and at 3-month to 6-month intervals thereafter. Adverse effects were carefully documented at each outpatient visit.…”

The nature of fibrous dysplasia

“…The unmineralized woven bone in long bones at sites where FD develops never matures into lamellar bone; and the local 'normal' mineralized bone adjacent to the lesion shows a relatively low mineral concentration. However, in persons with FD, the bones that are not affected by FD do not have osteomalacic changes [14,15]. In contrast to FD of long bones, in craniofacial FD the immature woven bone may undergo lamellation.…”