Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men?

Crabbe, Patricia; Goemaere, Stefan; Zmierczak, Hans‐Georg; Pottelbergh, I Van; Bacquer, Dirk De; Kaufman, Jean‐Marc

doi:10.1530/eje.1.02130

Cited by 18 publications

(17 citation statements)

References 45 publications

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“…Lorentzon et al [48] have concluded that leptin is a negative independent predictor of BMD, and Crabbe et al [49] have found that serum leptin is positively associated with bone loss. It seems, therefore, that further work is needed to clarify the role that the decrease in serum leptin after weight loss may play in the metabolic bone changes that develop simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Mineral Metabolism in Obese Patients Following Vertical Banded Gastroplasty

et al. 2008

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Weight reduction obtained in morbidly obese subjects 3 months after vertical banded gastroplasty increases bone turnover markers and decreases PTH secretion. Serum 25OHD levels rose. Therefore, no reasons for a metabolic bone disease related to hypovitaminosis D were readily apparent. However, an increase in bone turnover, which is generally regarded as a potential risk factor for osteoporosis, was observed. Further work is needed to clarify the importance of this turnover increase in the long run.

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Section: Discussionmentioning

confidence: 99%

Mineral Metabolism in Obese Patients Following Vertical Banded Gastroplasty

et al. 2008

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“…In a study population of 219 adult Korean males, carriers of the Gln223 allele had higher bone mineral density at the lumbar spine compared with subjects not carrying the allele (30). In 270 European men over 70 yr, however, no association was found between Gln223Arg and BMD changes at the hip and forearm (31). Therefore, the contribution of LEPR alleles to bone mass acquisition remains unknown.…”

Section: Eptin Has Recently Been Identified As An Importantmentioning

confidence: 99%

Bone Mass in Prepubertal Boys Is Associated with a Gln223Arg Amino Acid Substitution in the Leptin Receptor

Richert

Chevalley

Manen

et al. 2007

The Journal of Clinical Endocrinology &Amp; Metabolism

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Objective: The contribution of leptin to bone mass acquisition in humans remains unclear. We investigated the association of the Gln223Arg polymorphism in the leptin receptor gene (LEPR) with bone mineral content (BMC) and areal bone mineral density (aBMD) in prepubertal boys and LEPR interaction with vitamin D receptor (VDR) genotypes (Bsm1 and Fok1). Design:In a cross-sectional design with a longitudinal follow-up, dual-energy x-ray absorptiometry measurements at the lumbar spine, hip, femoral diaphysis, and radius were performed at baseline (mean age 7.4 Ϯ 0.4 yr) and 2 yr later in 222 healthy Caucasian males.Results: LEPR genotypes were significantly associated with baseline BMC at the hip (P ϭ 0.017), femur diaphysis (P ϭ 0.019), and radius (P ϭ 0.007) and with height (P ϭ 0.041) as well as with physical activity (P ϭ 0.016). Associations with height and BMC at femur diaphysis and radius remained significant after 2 yr. Significant differences in 2-yr bone mass gain at the spine and femur neck were also found among LEPR genotypes. In contrast, adjusting BMC for projected bone area (aBMD) and/or weight, height, and physical activity resulted in a weak association only at the femur (P ϭ 0.014 -0.054). VDR polymorphisms were not associated with BMC or aBMD, but significant interactions occurred between VDR Fok1 and LEPR genotypes. Conclusions:The LEPR Gln223Arg polymorphism was associated with bone mass in growing boys. The association, however, was markedly dependent on bone area, body size, and physical activity, in addition to VDR genetic variation, suggesting that the leptin system may modulate bone mass in humans mostly through indirect mechanisms. regulator of bone mass, first in mice (1) and then in sheep (2). Numerous experiments in rodents have clearly demonstrated that leptin exerts positive, anabolic effects on cortical bone and whole-body bone mineral mass (3-5). However, leptin deficiency has also been associated with increased, rather than decreased, trabecular bone volume density in mice (1, 6). Whether these apparently discordant results are due to a central inhibitory effect of leptin on bone formation and/or a stimulation of bone resorption through the ␤-adrenergic system (7, 8), or represent an adaptive response of the trabecular bone compartment to the cortical bone defect (9), remains unclear at present.In humans, the adipocyte-derived cytokine leptin is known to regulate food intake and energy balance, and thereby fat mass and weight, by activating a hypothalamic receptor (10). A number of studies have attempted to correlate circulating leptin levels with bone mineral density (BMD), yielding inconsistent results (11-23). Nevertheless, fat mass has recently been associated with gain in bone mass over 2 yr in prepubertal boys (24), raising the possibility of a positive relationship between leptin and early bone mass acquisition. Unfortunately, the variability of circulating leptin levels and its dependency on food intake might explain the discrepancy of the reported findings.The analysis of...

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“…У молодых китаянок, моло-дых корейских и европейских мужчин Gln223Arg-поли-морфизм был ассоциирован с пиком костной массы [28,35]. Среди 270 взрослых европейцев были выявлены ас-социация Gln223Arg-полиморфизма с костной щелоч-ной фосфатазой и отсутствие связи с МПКТ [36]. Интер-претация связи полиморфизмов гена LEPR с МПКТ за-труднена из-за плейотропных функций системы лепти-на.…”

Section: распределение аллелей и генотипов Lep (A19g) Lepr (Gln223arunclassified

LEPTIN A19G POLYMORPHISM AND LEPTIN RECEPTOR Gln223Arg AND Lys109Arg POLYMORPHISMSIN POSTMENOPAUSAL OSTEOPOROSIS

Krylov¹,

Krylov²,

Benevolenskaya³

et al. 2010

rsp

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Objective: to study an association of leptin (LEP) A19G polymorphism and leptin receptor (LEPR) Gln223Arg AND Lys109Arg polymorphisms with the predilection for postmenopausal osteoporosis (OP). Subjects and methods. PCR analysis was used to examine the polymorphisms among 428 women (254 patients with OP and 174 healthy women).The anthropometric, densitometric, and biochemical markers of bone remodeling and standard clinical and biochemical parameters were studied. Results. Statistically significant differences were found in the distribution of the genotypes of LEP A19G polymorphism between the women with OP and the controls (χ 2 = 9.41; p = 0.009). In the patients with OP, the 19GG genotype frequency was significantly higher than that in the controls [OR = 2.0;

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Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men?

Cited by 18 publications

References 45 publications

Mineral Metabolism in Obese Patients Following Vertical Banded Gastroplasty

Mineral Metabolism in Obese Patients Following Vertical Banded Gastroplasty

Bone Mass in Prepubertal Boys Is Associated with a Gln223Arg Amino Acid Substitution in the Leptin Receptor

LEPTIN A19G POLYMORPHISM AND LEPTIN RECEPTOR Gln223Arg AND Lys109Arg POLYMORPHISMSIN POSTMENOPAUSAL OSTEOPOROSIS

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