Howell S J, Berger G, Adams J E, Shalet S M
Department of Endocrinology, Christie Hospital NHS Trust, Manchester.
Clin Endocrinol (Oxf). 1998 Sep;49(3):397-402. doi: 10.1046/j.1365-2265.1998.00550.x.
Premature ovarian failure is associated with a reduction in bone mineral density. As survival rates following treatment for haematological malignancies improve, chemotherapy-induced ovarian failure is becoming more common. However, there are few data concerning the impact of this on bone mineral density (BMD). We have therefore measured the BMD in 33 women with ovarian failure following treatment with cytotoxic chemotherapy.
We studied 33 women who received combination chemotherapy for Hodgkin's disease (n = 27), non-Hodgkin's lymphoma (n = 4), sarcoma (n = 1) and acute myeloid leukaemia (n = 1). The mean (range) age of the subjects at the time of BMD measurement was 37.5 (24-50) years and the mean (median: range) duration of amenorrhoea was 49 (24: 5-277) months. Eleven women had received hormone replacement therapy (HRT) for a mean (range) duration of 25 (1-62) months. BMD was measured by single photon absorptiometry or single X-ray absorptiometry, and dual energy X-ray absorptiometry at the distal and proximal radius, the femoral neck and the lumbar spine, respectively. BMD was expressed as Z-scores and statistical analysis was performed using the Wilcoxon matched-pairs signed-rank test.
There was no significant reduction in BMD at the hip, spine or a forearm in the cohort as a whole, although there was a trend to reduce bone density at all sites. When patients who had received HRT were excluded from the analysis there were small reductions in mean BMD at all sites, but this was only statistically significant at the proximal forearm (Z-score = -0.65; P = 0.03). Mean BMD of the HRT-treated patients was normal at all sites. Only seven patients (21%) had a BMD Z-score < -2 at any site.
It is inappropriate to assume that ovarian failure from different aetiologies has a similar deleterious impact on the skeleton. Untreated premature ovarian failure following cytotoxic chemotherapy results in some reduction in bone mineral density, but this is of a minor degree and is less than that observed in other hypo-oestrogenic states. The reason for this is unclear but studies of residual hormone production in the cytotoxic-damaged ovary may provide an answer.
卵巢早衰与骨矿物质密度降低有关。随着血液系统恶性肿瘤治疗后生存率的提高，化疗所致的卵巢功能衰竭越来越常见。然而，关于其对骨矿物质密度（BMD）影响的数据很少。因此，我们测量了33例接受细胞毒性化疗后出现卵巢功能衰竭的女性的骨矿物质密度。
我们研究了33例接受联合化疗的女性，其中霍奇金病患者27例、非霍奇金淋巴瘤患者4例、肉瘤患者1例、急性髓系白血病患者1例。测量骨矿物质密度时，受试者的平均（范围）年龄为37.5（24 - 50）岁，闭经的平均（中位数：范围）持续时间为49（24：5 - 277）个月。11例女性接受了激素替代疗法（HRT），平均（范围）持续时间为25（1 - 62）个月。分别采用单光子吸收法、单能X线吸收法和双能X线吸收法测量桡骨远端和近端、股骨颈和腰椎的骨矿物质密度。骨矿物质密度以Z值表示，并采用Wilcoxon配对符号秩检验进行统计分析。
尽管整个队列中髋部、脊柱或前臂的骨矿物质密度没有显著降低，但所有部位都有骨密度降低的趋势。当排除接受激素替代疗法的患者后进行分析，所有部位的平均骨矿物质密度均有小幅降低，但仅在前臂近端具有统计学意义（Z值 = -0.65；P = 0.03）。接受激素替代疗法治疗的患者所有部位的平均骨矿物质密度均正常。只有7例患者（21%）在任何部位的骨矿物质密度Z值 < -2。
认为不同病因所致的卵巢功能衰竭对骨骼有相似的有害影响是不合适的。细胞毒性化疗后未经治疗的卵巢早衰会导致骨矿物质密度有所降低，但程度较轻，且低于其他低雌激素状态下观察到的情况。其原因尚不清楚，但对细胞毒性损伤卵巢中残余激素分泌的研究可能会给出答案。
