Serum osteocalcin has limited usefulness as a diagnostic marker for rickets.

UNLABELLED: Serum alkaline phosphatase (AP), the bone fraction of which is secreted by osteoblasts, is elevated in rickets. Both normal and elevated levels of serum osteocalcin (OC), a bone-specific marker secreted by osteoblasts, have been reported in rickets. Expression of the OC gene is enhanced by 1,25-dihydroxyvitamin D (1,25(OH)2D) in experimental models. This study assessed serum OC levels in 14 controls and 41 patients with active rickets divided into a phosphopenic (n = 20) and a calciopenic (n = 21) group. Phosphopenic subjects were older (9.5 versus 5.7 years, P = 0.03) with higher median serum calcium level (2.35 versus 2.16 mmol/l, P = 0.0002) and serum 25-hydroxyvitamin D level (15.4 versus 10.4 ng/l, P = 0.003); and lower serum phosphate (0.80 versus 1.51 mmol/l, P = 0.0001), serum 1,25(OH)2D (43.0 versus 95.6 pg/ml, P = 0.0001) and intact serum parathyroid hormone level (45.0 versus 141.5 ng/l, P = 0.01) than calciopenic subjects. There were no differences in median serum AP (774 versus 1430 IU/l, P = 0.17) and OC (14.5 versus 13.4 ng/ml, P = 0.6) between the two groups. The mean OC value for the 41 rickets subjects was 15.1 +/- 6.2 ng/ml and 17.4 +/- 7.8 ng/ml for the 14 control subjects. In the face of markedly elevated serum AP levels in the rickets subjects, all of the serum OC values in the study fell within two standard deviations of the mean for normals. There was no association between serum OC and 1,25-(OH)2D in either the phosphopenic or the calciopenic group. CONCLUSION: These results show that serum osteocalcin levels are not elevated in all forms of active rickets and that, unlike serum alkaline phosphatase, serum osteocalcin cannot be used in the diagnosis of rickets.

Bone disease in African children with slipped capital femoral epiphysis: histomorphometry of iliac crest biopsies.

African teenagers with slipped capital femoral epiphysis (SCFE) not infrequently also have genu valgum (knock-knee). Because we had previously demonstrated metabolic bone disease attributable to dietary calcium deficiency in black teenagers with genu valgum, we examined 29 black teenagers (15 male, 14 female) with SCFE for metabolic bone disease. Each patient had an iliac crest bone biopsy taken (after double tetracycline labeling) for routine histomorphometry, and blood and urine samples for bone biochemistry. Spinal bone mineral density was measured in 13 patients. Compared to reported data, we found our patients to be sexually more immature, older, at least as obese, and to have more severe and more frequently bilateral hip disease. Eighty percent of the children took dairy products only once or twice a week or less frequently, and 37.9% had genu valgum. Compared with race- and age-matched South Africans, bone biopsies in our patients showed lower bone volume (BV/TV, p = 0.0003), wall thickness (p = 0.0002), and trabecular thickness (Tb.Th, p = 0.0002), and a tendency to greater trabecular spacing (Tb.Sp, p = 0.053). Lower osteoid volume (OV/BV, p = 0.0001), osteoid surface (OS/BS, p = 0.0001), osteoid thickness (O.Th, p = 0.0002), double labeled surface (dLS/BS, p = 0.029), and bone formation rate (BFR/BS, p = 0.037) suggested poorer bone forming capacity in our patients. No evidence of hyperparathyroid bone disease or osteomalacia was found. BV/TV was below the reference range (14.2%) in 65.5% of cases; these patients had lower values for Tb.Th (p = 0.037) and Tb.N (p = 0.0003), greater Tb.Sp (p = 0.0002), a tendency to lower adjusted apposition rate (Aj.AR, p = 0.057), and had had less frequent intake of dairy products than those with normal BV/TV (p = 0.024). Furthermore, months since menarche correlated with histomorphometric variables BV/TV (r = 0.667, p = 0.009), Tb.Th (r = 0.745, p = 0.002), Tb.Sp (r = -0.549, p = 0.042), O.Th (r = 0.784, p = 0.0009), and Aj.AR (r = 0.549, p = 0.042). The correlation between Tb.Th and spinal bone mineral content (r = 0.656, p = 0.015) suggests that the reduced trabecular thickness reflected a generalized bone condition. A greater than normal proportion of patients had spinal bone mineral density values below -1 standard deviation (SD) of the mean (osteopenia) (p = 0.001). Patients tested for parathyroid hormone and 25-hydroxyvitamin D levels were found to have normal values. Parathyroid hormone correlated with Aj.AR (r = 0.661, p = 0.038) and serum phosphorus (r = -0.764, p = 0.010). We conclude that sexual immaturity and possibly past dietary calcium deficiency contributed to osteopenia, and that this, together with obesity, led to the development of more severe and more frequently bilateral SCFE in our patients than in reported series of black and white children.

Differences in mineral homeostasis, volumetric bone mass and femoral neck axis length in black and white South African women.

In South Africa, appendicular and lumbar spine bone mineral density (BMD) have been found to be similar in black and white women. However, femoral BMD has been found to be higher in black than in white women. Two different techniques were used to recalculate BMD to eliminate the possible confounding influence of ethnic differences in height on areal BMD measurements. Volumetric bone mineral apparent density (BMAD) values were calculated and bone mineral content (BMC) was corrected for body and bone size. This report analyses differences in BMD (corrected for height and weight), BMAD, BMC (corrected for body and bone size), femoral neck axis length (FNAL), mineral homeostasis and bone turnover (BT) in a group of 20 to 49-year-old premenopausal (105 whites and 74 blacks) and 45 to 64-year-old postmenopausal (50 whites and 65 blacks) female South African nurses. The corrected BMD and BMC findings were congruous, showing that both pre- and postmenopausal blacks and whites have similar distal radius and lumbar spine bone mass but that whites have lower femoral neck bone mass than blacks. In contrast, BMAD findings suggest that pre- and postmenopausal whites have lower bone mass at the lumbar spine and femoral neck than blacks but similar bone mass at the distal radius to blacks. There is a greater rate of decline in BMD in postmenopausal whites than in blacks. BMD at the femoral neck was 12.1% lower in premenopausal whites and 16.5% lower in postmenopausal whites than in blacks. There was a positive association between femoral neck BMD and weight in premenopausal blacks (R2 = 0.5, p = 0.0001) but not in whites. Blacks had shorter FNAL than whites in both the pre- and post-menopausal groups. Blacks had lower serum 25-hydroxyvitamin D (25-(OH)D) and higher 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels than whites. There were no ethnic differences in biochemical markers of bone formation (serum alkaline phosphatase and osteocalcin) or bone resorption (urine hydroxyproline and pyridinoline), or in dietary calcium intake in either the pre- or postmenopausal groups. In the postmenopausal group, whites had higher ionized serum calcium (p = 0.003), similar serum albumin, lower serum parathyroid hormone (p = 0.003) and higher urinary calcium excretion (p = 0.0001) than blacks. These results suggest that the higher peak femoral neck BMD in South African blacks than in whites might be determined by greater weight-bearing in blacks and that the significantly lower femoral neck BMD in postmenopausal whites than in blacks is determined by lower peak femoral neck BMD and a faster postmenopausal decline in BMD in whites. The higher incidence of femoral neck fractures in South African whites than in blacks is probably determined by the lower femoral neck BMD and longer FNAL in whites. The greater rate of decline in BMD in postmenopausal whites than in blacks is associated with an increase in urinary calcium excretion in whites. Measurement of biochemical markers of BT has not contributed to the understanding of ethnic differences in BMD and skeletal metabolism in our subjects.

Ethnic differences in bone density in female South African nurses.

In the United States, the higher prevalence of osteoporosis and the higher incidence of fractures in whites than in blacks may be attributed to the finding of lower bone density (BD) in both white children and adults. In South Africa, osteoporosis and fractures also occur more frequently in whites than in blacks. Appendicular BD has been found to be similar in black and white children in South Africa, but there is little information available on BD of adults in South Africa. This cross-sectional study aimed to assess changes in BD with age in adult females in South Africa and to assess possible differences in peak BD and in the rate of postmenopausal bone loss between blacks and whites. Data for 180 black and 184 white female nurses aged 20-64 years were analyzed. The distal radius bone density (RBD) was measured by single photon absorptiometry. The lumbar spine bone density (SBD) and the femur bone density (FBD) were measured by dual-energy X-ray absorptiometry. Blacks were shorter than whites (p = 0.0001), and blacks' weight, body mass index, and skinfold thickness increased with age. Peak SBD and RBD were similar in blacks and whites, but peak FBD was higher in blacks (p = 0.0001). This ethnic difference in peak FBD became apparent in the fourth decade. Peak FBD was similar in black and white subjects with normal body mass indices (p = 0.09), but in overweight subjects peak FBD was higher in blacks than in whites (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Rheumatic fever prophylaxis in South Africa--is bicillin 1,2 million units every 4 weeks appropriate?

Rheumatic fever is a major health problem in South Africa. Although intramuscular benzathine penicillin (bicillin) 1.2 million units (MU) every 4 weeks is widely used for secondary prophylaxis, studies in other countries have shown a recurrence rate of 3-8% over 5-6 years in patients on this regimen. It has been recommended that serum penicillin concentrations should be maintained above 0.02 mg/ml to prevent such recurrences. The World Health Organisation (WHO) and the American Heart Association have recommended since 1988 that patients in high-risk areas for the development of rheumatic fever should receive benzathine penicillin 1.2 MU every 3 weeks rather than every 4. The aims of this study were, firstly, to determine the prevalence of serum penicillin concentrations below 0.02 micrograms/ml in rheumatic fever patients on benzathine penicillin 1.2 MU 4-weekly and, secondly, to study the effect of increasing the dose of 1.8 MU 4-weekly in patients with subtherapeutic concentrations. Forty-five of 51 rheumatic fever patients (88%) in this study on benzathine penicillin 1.2 MU 4-weekly had low serum penicillin concentrations (< 0.02 micrograms/ml) at the end of the 4th week after the injection. Penicillin was detected in the urine of 30 of the 45 patients (67%) with low concentrations, suggesting that such patients have tissue-bound penicillin which might be important in preventing rheumatic fever. The 15 patients (33%) with subtherapeutic serum penicillin concentrations and no detectable penicillin in the urine could be at very high risk for recurrent attacks of rheumatic fever. Fourteen of 29 patients (48%) given the higher dose of benzathine penicillin (1.8 MU 4-weekly) had subtherapeutic serum penicillin concentrations at the end of the 4th week after the injection, but in all 29 penicillin was detected in the urine. Review of our present policy of secondary prophylaxis for rheumatic fever is necessary. Concentrated preparations of benzathine penicillin (600,000 U/ml) are not available in South Africa; administration of a higher dose (1.8 MU) 4-weekly would therefore require a double injection, which could affect compliance adversely. We recommend that rheumatic fever patients in our area should receive benzathine penicillin 1.2 MU 3-weekly as recommended by the WHO until strategies for secondary prophylaxis have been evaluated further.