Sanyal Arunik, Hoey Kelley A, Mödder Ulrike I, Lamsam Jesse L, McCready Louise K, Peterson James M, Achenbach Sara J, Oursler Merry Jo, Khosla Sundeep
Endocrine Research Unit, Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
J Bone Miner Res. 2008 May;23(5):705-14. doi: 10.1359/jbmr.071212.
The mechanism(s) by which sex steroids regulate bone turnover in humans are unclear, and recent studies have suggested that follicle-stimulating hormone (FSH) may play an important role in regulating bone resorption.
Fifty-nine men (median age, 69 yr) underwent suppression of sex steroids using a gonadotropin-releasing hormone (GnRH) agonist and aromatase blocker and were replaced with testosterone (T; 5 mg/d) and estradiol (E; 37.5 microg/d). After assessment of bone resorption markers (serum C-terminal telopeptide of type I collagen [CTX] and TRACP5b), they were randomized to sex steroid deficiency (-T, -E), E alone (-T, +E), T alone (+T, -E), or both (+T, +E) and restudied 3 wk later. Bone marrow aspirates were obtained to isolate osteoblastic, T, and monocytic cells using magnetic-activated cell sorting.
Serum CTX and TRACP5b increased significantly (by 71% and 15%, p < 0.01 and < 0.001, respectively) in the -T, -E group, and these increases occurred despite a 60% suppression of serum FSH levels (p < 0.001) caused by the GnRH agonist. There were significant E (but not T) effects on preventing increases in serum CTx and TRACP levels. There was a nonsignificant trend (p = 0.122) for E to suppress RANKL mRNA levels in bone marrow osteoblastic cells. Changes in mRNA levels for other cytokines (TNF-alpha, interleukin (IL)-1alpha, IL-1beta, IL-1ra, IFN-gamma) in bone marrow cells were not significant.
E has greater suppressive effects on bone resorption than T, and increased bone resorption after sex steroid deficiency can occur independently of changes in FSH secretion. E effects on bone resorption may be mediated by regulation of RANKL production by osteoblastic cells, although further studies using more highly purified cells may reduce the variability of the mRNA measurements and allow for clearer definition of the mediators of sex steroid action in vivo.
性类固醇调节人类骨转换的机制尚不清楚，最近的研究表明促卵泡激素（FSH）可能在调节骨吸收中起重要作用。
59名男性（中位年龄69岁）使用促性腺激素释放激素（GnRH）激动剂和芳香化酶抑制剂抑制性类固醇，并用睾酮（T；5mg/d）和雌二醇（E；37.5μg/d）进行替代。在评估骨吸收标志物（血清I型胶原C端肽[CTX]和TRACP5b）后，他们被随机分为性类固醇缺乏组（-T，-E）、单独使用E组（-T，+E）、单独使用T组（+T，-E）或两者皆用组（+T，+E），并在3周后重新进行研究。通过磁激活细胞分选获取骨髓抽吸物以分离成骨细胞、T细胞和单核细胞。
-T，-E组血清CTX和TRACP5b显著增加（分别增加71%和15%，p<0.01和<0.001），尽管GnRH激动剂导致血清FSH水平抑制了60%（p<0.001），但这些增加仍发生了。E（而非T）在预防血清CTX和TRACP水平升高方面有显著作用。E抑制骨髓成骨细胞中RANKL mRNA水平有不显著的趋势（p = 0.122）。骨髓细胞中其他细胞因子（TNF-α、白细胞介素（IL）-1α、IL-1β、IL-1ra、IFN-γ）的mRNA水平变化不显著。
E对骨吸收的抑制作用比T更强，性类固醇缺乏后骨吸收增加可能独立于FSH分泌的变化而发生。E对骨吸收的作用可能通过调节成骨细胞产生RANKL来介导，尽管使用更高纯度细胞的进一步研究可能会降低mRNA测量的变异性，并更清楚地定义体内性类固醇作用的介质。
