Leptin stimulates osteoblastic cell proliferation, differentiation and mineralisation and inhibits osteoclast generation; leptin secretion and bone turnover are altered in adult growth hormone deficiency, a condition associated with osteoporosis. The aim of this study was to investigate leptin circadian rhythm and its association with bone turnover in untreated AGHD and following growth hormone replacement (GHR).
We sampled peripheral venous blood at half-hourly intervals in 12 AGHD patients (6 men) over a 24 hour period (1400-1400h) before then after 1 and 12 months of GHR. Cross-correlation analysis was used to determine the relationship between leptin, type 1 collagen C-telopeptide (CTX) and procollagen type1 amino-terminal propeptide (PINP).
In untreated AGHD leptin/CTX and leptin/PINP showed maximum cross-correlation when CTX (r=0.86) and PINP (r=0.82) were lagged by 0 time points. Maximum leptin/CTX(r=0.85) and leptin/PINP(r=0.85) correlations following 1 month of GHR were also observed at 0 lags. After 12 months of GHR, the point of maximum leptin/CTX cross-correlation was observed when the CTX series was lagged by 2 time points, or 1 h, after the leptin series(r=0.88), suggesting that the change in leptin now preceded the change in CTX. Leptin/PINP cross-correlation at 12 months was maximum at 0 lags(r=0.85). Leptin decreased from 2.05plus/minus0.04 nmol/liter to 1.65plus/minus0.03nmol/liter at 1 month and increased significantly to 2.04plus/minus0.04nmol/liter from 1to 12 months. 24-h mean CTX increased significantly at 1 month (0.21 plus/minus0.01ng/ml;P<0.001) and increased further at 12 months (0.37plus/minus0.01ng/ml;P<0.001) compared with baseline (0.18plus/minus0.01ng/ml). PINP increased at 1 month (52.0plus/minus1.3microg/liter;P<0.001) and 12 months (70.8plus/minus1.3microg/liter;P<0.001) compared to baseline (40.8plus/minus1.2 microg/liter)
Our results suggest a common controlling factor for the secretion of leptin and the markers of bone turnover and indirect coupling possibly via previously demonstrated in vitro effects of leptin on osteoblast and osteoclast function. Observed changes in leptin concentration may in part, be indirectly responsible for the observed increase in bone turnover following GHR in AGHD.
22 - 24 Mar 2004
British Endocrine Societies