早發性停經與初次骨折年齡之相關性分析：回溯性世代研究

研究背景與目的停經後雌激素快速下降會加速骨質流失並提高骨折風險；若停經時間提前，女性將更早暴露於低雌激素狀態，可能導致初次骨折提前發生。然而，早發性停經是否在同時考量骨質密度與共病因素後，仍與初次骨折年齡提前具有獨立關聯，仍有待釐清。本研究以回溯性世代設計，探討早發性停經與初次骨折年齡之關聯。會使「初次骨折」更早出現且存在穩定關聯，以及在同時考量骨質密度與共病因素後，是否仍可被視為獨立風險因子，臨床上仍需以實證資料加以釐清。本研究以回溯性世代設計，探討早發性停經與初次骨折年齡的關聯，並以多變項調整及骨質密度配對敏感性分析，檢驗結果之穩健性。研究方法本研究使用院內資料庫建立停經女性族群，以骨密度檢查日期為追蹤起點，追蹤至首次骨折、死亡或資料截止日。排除停經前既往骨折史、重大共病及基線骨密度不符者後，納入 1,529 人進行分析。暴露因子為停經年齡，定義早發性停經（EMP）為 <45 歲，正常停經（NMP）為 ≥45 歲。主要結果為追蹤期間之首次骨折，並以是否於 ≤50、≤55、≤60、≤65 歲前發生首次骨折作為早發性骨折指標。以羅吉斯迴歸估計勝算比，並校正基線 T-score、共病與用藥因素；另進行 T-score 1:7 配對之敏感性分析。研究結果主要分析族群中，EMP 組 68 人，NMP 組 1,461 人。EMP 組在較低年齡即發生首次骨折的比例顯著高於 NMP 組，且差異在年齡較低之族群尤為明顯：≤50 歲（11.8% vs 0.8%）、≤55 歲（16.2% vs 3.6%）、≤60 歲（26.5% vs 12.4%）、≤65 歲（39.7% vs 26.8%）。在校正基線骨質密度與相關共病及用藥因素後，早發性停經仍與早發性骨折呈顯著相關，其 adjusted OR 隨年齡門檻遞減，但皆達統計顯著。於 T-score 1:7 配對後之分析中，EMP 與初次骨折年齡提前之關聯仍維持一致方向與顯著性，顯示該關聯並非僅由骨質密度差異所驅動。結論早發性停經（<45 歲）與初次骨折提早發生具有顯著且穩定的關聯，即使在同時考量骨質密度、共病與用藥因素後，仍可視為早發性骨折的獨立危險因子。臨床實務上。關鍵詞：早發性停經、初次骨折年齡、早發性骨折、骨質密度、T-score、回溯性世代研究

Background and ObjectiveAfter menopause, the rapid decline in estrogen accelerates bone loss and increases fracture risk. When menopause occurs at an earlier age, women are exposed sooner to a hypoestrogenic state, which may lead to an earlier occurrence of the first fracture. However, it remains unclear whether early menopause is independently associated with an earlier age at first fracture after accounting for bone mineral density (BMD) and comorbid conditions. This retrospective cohort study aimed to investigate the association between early menopause and the age at first fracture.MethodsUsing an institutional clinical database, we established a cohort of postmenopausal women. Follow-up commenced on the date of baseline bone mineral density assessment and continued until the occurrence of the first fracture, death, or the end of data availability. Participants with a history of fracture before menopause, major premenopausal comorbidities, or inconsistent baseline BMD data were excluded. A total of 1,529 women were included in the analysis. The exposure variable was age at menopause, with early menopause (EMP) defined as menopause before 45 years of age and normal-age menopause (NMP) as menopause at or after 45 years. The primary outcome was the first fracture during follow-up. Early fracture was operationalized as the occurrence of the first fracture before specific age thresholds (≤50, ≤55, ≤60, and ≤65 years). Logistic regression models were used to estimate odds ratios (ORs), adjusting for baseline T-score, comorbidities, and medication use. Sensitivity analyses were conducted using 1:7 T-score matching between EMP and NMP groups. ResultsAmong the study population, 68 women were classified as EMP and 1,461 as NMP. The proportion of women experiencing a first fracture at younger ages was significantly higher in the EMP group, with the greatest differences observed at earlier age thresholds: ≤50 years (11.8% vs. 0.8%), ≤55 years (16.2% vs. 3.6%), ≤60 years (26.5% vs. 12.4%), and ≤65 years (39.7% vs. 26.8%). After adjustment for baseline BMD, comorbidities, and medication use, early menopause remained significantly associated with early fracture, with adjusted ORs decreasing across increasing age thresholds but remaining statistically significant. In the T-score–matched analysis, the association between early menopause and an earlier age at first fracture persisted with consistent direction and statistical significance, indicating that this relationship was not solely attributable to differences in bone mineral density.ConclusionsEarly menopause (<45 years) is significantly and consistently associated with an earlier occurrence of the first fracture and remains an independent risk factor even after accounting for bone mineral density, comorbidities, and medication use. From a clinical perspective, women with early menopause should be considered a high-risk population and may benefit from earlier fracture risk assessment and preventive interventions.