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Leptin Effects Bone Density Independent of Hormone Replacement Therapy

Leptin may determine the extent of bone resorption, but without any mediation by leptin on the effect of estradiol or tibolone on bone metabolism, in healthy, postmenopausal women who are not taking hormone replacement therapy.

Leptin may also have an important mediating role in maintaining bone mass in obese subjects as both bone density and leptin levels depend on body weight. As well, women have 2- to 3-fold higher level of leptins, independent of adiposity. Therefore, oestrogen might play a stimulating role in leptin secretion.

Christian Roux from the Centre d'Evaluation des Maladies Osseuses, Département de Rhumatologie, Hôpital Cochin (AP-HP), Université René Descartes, Paris, France, undertook a prospective, randomised, double-blind study to investigate the effects of leptin on bone metabolism in 121 healthy postmenopausal women aged more than 45 years. Women with a body mass index below 19 or over 27 kg/m² were excluded from the study.

The authors measured bone mineral density (BMD) at the spine and the hip, fasting serum leptin, and osteocalcin and urinary excretion of C-terminal crosslinking telopeptide of type I collagen (CTX), as markers of bone formation and resorption to study the relationships between serum leptin and bone metabolism.

The researchers randomised the 34 subjects to 2.5 mg tibolone, 45 women to 1.25 mg tibolone, and 42 participants to 2 mg estradiol plus 1 mg norethindrone acetate. All women received a daily supplementation of 500 mg of calcium with a meal during a follow-up duration of 2 years.

The results show that at baseline, serum leptin showed a positive relationship with spine (r = 0.21, P = .02) and total hip (r = 0.26, P = .0044) BMD and negative association with CTX (r = -0.38, P < .0001) and osteocalcin (r = 0.21, P = .025). The correlation between serum leptin and CTX remained even after adjustment for BMI and for fat mass.

Women in the highest levels of leptin showed 11% higher total hip (P = .0039) and lumbar spine BMD (P = .016), 21% lower osteocalcin (P = .01), and 38% lower CTX (P = .0005) than women with least leptin levels (P < .05).

Serum leptin levels increased significantly (+14.7 ± 47.3%, P = .019) during the treatment, but without significant difference between the groups. However, the increase correlated with the increase in body weight (r = 0.46, P < 10^-4 without any correlation between the changes in leptin and the changes in bone parameters.

The researchers postulated that disappearance of correlation between leptin and bone density and the persistence of the correlation between leptin and CTX suggested that leptin is not directly related to bone mass in women, but may play an important role in determining bone turnover.

The authors concluded that leptin may play an important role as a determinant of bone resorption in healthy, non-obese, untreated postmenopausal women, but the effects of HRT and tibolone on bone turnover and BMD are not explained by changes in leptin levels.













Bone 2003;33:5:847-852. "Serum leptin as a determinant of bone resorption in healthy postmenopausal women"

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