Uzzan B, Campos J, Cucherat M, Nony P, Boissel J P, Perret G Y
Hôpital Avicenne, Centre Hospitale Universitaire Paris Nord, France.
J Clin Endocrinol Metab. 1996 Dec;81(12):4278-89. doi: 10.1210/jcem.81.12.8954028.
Osteoporosis is the main cause of spine and hip fractures. Morbidity, mortality, and costs arising from hip fractures have been well documented. Thyroid hormones (TH) are widely prescribed, mainly in the elderly. Some studies (but not all) found a deleterious effect of suppressive TH therapy on bone mass. These conflicting data raised a controversy as to the safety of current prescribing and follow-up habits, which, in turn, raised major health-care issues. To look for a detrimental effect on bone of TH therapy, we performed a meta-analysis (by pooling standardized differences, using a fixed effect model) of all published controlled cross-sectional studies (41, including about 1250 patients) concerning the impact of TH therapy on bone mineral density (BMD). Studies with women receiving estrogen therapy were excluded a priori, as were studies with a high percentage of patients with postoperative hypoparathyroidism, when no separate data were available. We decided to stratify the data according to anatomical site, menopausal status, and suppressive or replacement TH therapy, resulting in 25 meta-analysis on 138 homogeneous subsets of data. The main sources of heterogensity between studies that we could identify were replacement or suppressive TH therapy, menopausal status, site (lumbar spine, femoral neck, Ward's triangle, greater trochanter, midshaft and distal radius, with various percentages of cortical bone), and history of hyperthyroidism, which has recently been found to impair bone mass in a large epidemiological survey. To improve homogeneity, we excluded a posteriori 102 patients from 3 studies, who had a past history of hyperthyroidism and separate BMD data, thus allowing assessment of the TH effect in almost all 25 subset meta-analyses. However, controls were usually not matched with cases for many factors influencing bone mass, such as body weight, age at menarche and at menopause, calcium dietary intake, smoking habits, alcohol intake, exercise, etc. For lumbar spine and hip (as for all other sites), suppressive TH therapy was associated with significant bone loss in postmenopausal women (but not in premenopausal women), whereas, conversely, replacement therapy was associated with bone loss in premenopausal women (spine and hip), but not in postmenopausal women. The detrimental effect of TH appeared more marked on cortical bone than on trabecular bone. Only a large long term prospective placebo-controlled trial of TH therapy (e.g. in benign nodules) evaluating BMD (and ideally fracture rate) would provide further insight into these issues.
骨质疏松症是脊柱和髋部骨折的主要原因。髋部骨折导致的发病率、死亡率及费用已有充分记录。甲状腺激素（TH）被广泛应用，主要用于老年人。一些研究（但并非全部）发现抑制性TH治疗对骨量有有害影响。这些相互矛盾的数据引发了关于当前用药及随访习惯安全性的争议，进而引发了重大的医疗保健问题。为探究TH治疗对骨骼的有害影响，我们对所有已发表的关于TH治疗对骨密度（BMD）影响的对照横断面研究（41项，包括约1250例患者）进行了荟萃分析（通过合并标准化差异，采用固定效应模型）。接受雌激素治疗的女性的研究以及术后甲状旁腺功能减退患者比例高且无单独数据的研究被事先排除。我们决定根据解剖部位、绝经状态以及抑制性或替代性TH治疗对数据进行分层，从而对138个同质数据子集进行了25项荟萃分析。我们能够识别的研究之间异质性的主要来源包括替代性或抑制性TH治疗、绝经状态、部位（腰椎、股骨颈、沃德三角、大转子、骨干和桡骨远端，皮质骨比例各不相同）以及甲状腺功能亢进病史，最近在一项大型流行病学调查中发现甲状腺功能亢进病史会损害骨量。为提高同质性，我们事后从3项研究中排除了102例有甲状腺功能亢进病史且有单独BMD数据的患者，从而几乎在所有25个子集荟萃分析中都能评估TH的影响。然而，对于许多影响骨量的因素，如体重、初潮年龄和绝经年龄、钙饮食摄入量、吸烟习惯、饮酒量、运动等，对照组通常与病例组不匹配。对于腰椎和髋部（以及所有其他部位），抑制性TH治疗与绝经后女性的显著骨量丢失相关（但绝经前女性无此情况），相反，替代疗法与绝经前女性（脊柱和髋部）的骨量丢失相关，但绝经后女性无此情况。TH对皮质骨的有害影响比对小梁骨更为明显。只有一项大型的长期前瞻性TH治疗安慰剂对照试验（例如针对良性结节）评估BMD（理想情况下还有骨折率）才能进一步深入了解这些问题。
