Abstract 23

Introduction: Osteocalcin(OC), a bone matrix protein, is widely used as a marker of osteoblastic activity and hence bone formation(BF) but functionally appears to modulate bone resorption(BR). Bone OC is decreased in rachitic chicks. In rachitic rats, low serum OC is associated with disproportionately lower bone OC. OC-deficient bone is poorly resorbed both in vitro and in vivo. Both low-normal and elevated serum OC levels have been reported in rickets in humans.

Methods: Serum OC was assessed in 14 controls and 41 patients with untreated rickets divided into a phosphopenic (n=20) and a calciopenic(n=21) group. Serum alkaline phosphatase(AP) and phosphate(Pi) were measured by autoanalyser, calcium(Ca) by atomic absorption spectrometry, OC by CIS biointernational RIA kit and vitamin D metabolites by competitive protein-binding assay.

Results: Phosphopenic subjects had higher serum Ca (2.37 vs 2.09mmol/l,p=0.0002), lower Pi (0.83 vs 1.46mmol/l,p=0.0001) and 1,25(OH)2D (36.4 vs 110.5pg/ml,p=0.0001), and similar AP (1597 vs 1154 IU/l,p=0.17) and OC (15.6 vs 14.6ng/ml,p=0.6) than calciopenic subjects. Mean serum OC was 15.1±6.2 ng/ml for the 41 subjects and 17.4±7.8 ng/ml for the controls. Seven percent of the subject OC values were >2 standard deviations (SD), 79% within 2 SD and 14%<2 SD of controls, with no association between serum OC and 1,25-(OH)2D in the calciopenic group.

Discussion: In this study, serum OC levels are low-normal in all forms of untreated rickets, in contrast to high serum AP and despite high serum 1,25(OH)2D. Since low serum OC is associated with low bone OC, these data suggest that overgrowth of cranial and metaphyseal rachitic bone might be due to bone OC depletion with diminished BR. A novel approach to optimising peak bone mass by altering BF/BR balance without compromising bone structural integrity is suggested.