Fat mass is an important determinant of bone density, but the mechanism of this relationship is uncertain. Leptin, as a circulating peptide of adipocyte origin, is a potential contributor to this relationship. Recently it was shown that intracerebroventricular administration of leptin is associated with bone loss, suggesting that obesity should be associated with low bone mass, the opposite of what is actually found. Since leptin originates in the periphery, an examination of its direct effects on bone is necessary to address this major discrepancy.Leptin (>10 11 M) increased proliferation of isolated fetal rat osteoblasts comparably with IGF-I, and these cells expressed the signalling form of the leptin receptor. In mouse bone marrow cultures, leptin (d10 11 M) inhibited osteoclastogenesis, but it had no effect on bone resorption in two assays of mature osteoclasts. Systemic administration of leptin to adult male mice (20 injections of 43 µg/day over 4 weeks) reduced bone fragility (increased work to fracture by 27% and displacement to fracture by 21%, P<0·001). Changes in tibial histomorphometry were not statistically significant apart from an increase in growth plate thickness in animals receiving leptin. Leptin stimulated proliferation of isolated chondrocytes, and these cells also expressed the signalling form of the leptin receptor.It is concluded that the direct bone effects of leptin tend to reduce bone fragility and could contribute to the high bone mass and low fracture rates of obesity. When administered systemically, the direct actions of leptin outweigh its centrally mediated effects on bone, the latter possibly being mediated by leptin's regulation of insulin sensitivity.

The assessment of vertebral bone mineral density (BMD) in the anterio-posterior projection has become widely used in the management and prevention of osteoporosis. Recently, it has been demonstrated that the presence of spinal osteophytes has a major impact on measured BMD in men, thus casting doubt on the value of these BMD measurements. We have assessed the impact of osteophytic and aortic calcification on spinal and femoral BMD measurements in 130 normal postmenopausal women, aged 45-71 yr. Lateral lumbar spine radiographs were obtained in all subjects and graded separately (0-3) for osteophytes and aortic calcification. Both forms of calcification increased with age, and BMD of all sites was correlated positively with body weight and negatively with age. The correlation coefficients between BMD and calcification scores were nonsignificant. Multiple regression analysis, including weight, age, and calcification scores, demonstrated a small but significant effect of osteophyte score on lumbar BMD (partial r2 = 0.04; P = 0.012) and a similar trend for Ward's triangle and the trochanteric region (partial r2 = 0.02; P less than 0.06). The aortic calcification score remained nonsignificant. It is concluded that the influence of spinal osteophytes on lumbar BMD in postmenopausal women is substantially less than that in men and is, therefore, unlikely to interfere with BMD estimation in most subjects. The relationship between proximal femoral BMD and osteophyte score suggests a real relationship between skeletal density and degenerative joint disease, as has been demonstrated by others.

Peptides purified by HPLC are often in the form of a trifluoroacetate (TFA) salt, because trifluoroacetic acid is used as a solvent in reversed-phase HPLC separation. However, the potential effects of this contaminant in culture systems have not been addressed previously. TFA (10(-8) to 10(-7) M) reduced cell numbers and thymidine incorporation into fetal rat osteoblast cultures after 24 h. Similar effects were found in cultures of articular chondrocytes and neonatal mouse calvariae, indicating that the effect is not specific to one cell type or to one species of origin. When the activities of the TFA and hydrochloride salts of amylin, amylin-(1-8), and calcitonin were compared in osteoblasts, cell proliferation was consistently less with the TFA salts of these peptides, resulting in failure to detect a proliferative effect or wrongly attributing an antiproliferative effect. This finding is likely to be relevant to all studies of purified peptides in concentrations above 10(-9) M in whatever cell or tissue type. Such peptides should be converted to a hydrochloride or biologically equivalent salt before assessment of their biological effects is undertaken.

Background-Cystic fibrosis is a multisystem disease characterised by chronic pulmonary sepsis and malnutrition. To ascertain whether osteoporosis is a feature of cystic fibrosis in adult patients, total body and regional bone mineral density (BMD) There is potential for decreased bone mineral density (BMD) in patients with cystic fibrosis as a result of the vitamin and mineral malabsorption, hypogonadism, malnutrition, and relative inactivity which characterise the disease. Previous studies to assess bone mass in patients with cystic fibrosis have produced conflicting results. Three studies have been undertaken using single photon absorptiometry. Normal metacarpal bone mineral content was found in a group of 18 patients aged 6-18 years.' Distal forearm bone mineral content was normal in six patients under the age of 10 years but the same authors found that 60% of subjects over the age of 15 years exhibited reduced bone mineral content at the same site.2 In this group of adolescents the reduction in bone mass correlated with the degree of observed weight reduction. The only published study on bone mass in adult patients with cystic fibrosis reported a 14% reduction in distal forearm bone mineral content in 21 subjects of average age 21 years.3More recently Gibbens et al used quantitative computed tomography to compare the lumbar spinal BMD of a predominantly paediatric population of patients with cystic fibrosis (average age 12 years) with that of age matched, normal controls.4 In addition to a 10% reduction in spinal BMD, they found that disease severity as measured by the Schwachman scoring system and poor nutritional state as assessed by anthropometric measurements (skin thickness, forearm circumference) correlated with BMD.

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