Osteoporosis May Increase Risk of Dry AMD in Women

Clinicians should be more vigilant about AMD development in post-menopausal women, researchers argue, given the expected decline in estrogen, which exerts a protective effect against the disease. Photo: Brian Chou, OD. Click image to enlarge. In a recent study published in Experimental Gerontology, researchers systematically investigated the association and potential causal relationship between osteoporosis and age-related macular degeneration (AMD), including its subtypes, using both meta-analysis of observational studies and bidirectional two-sample Mendelian randomization (MR). They found that osteoporosis may increase the risk of AMD in women, especially elderly women, and they also found that both conditions share biological mechanisms, including vitamin D deficiency and dysregulated calcium homeostasis.The three included studies in their meta-analysis consisted of two cross-sectional investigations and one cohort study totaling 58,057 participants representing both Asian and European ethnicities. Analysis indicated that osteoporosis increases the risk of AMD in women, and elderly women should be considered at potential high risk for dry AMD. The odds ratio for dry AMD risk was 1.26 among osteoporosis patients.Collectively, these findings indicate that vitamin D deficiency—common in osteoporosis patients—may impair the barrier function of retinal pigment epithelial cells, laying a structural foundation for the development of AMD. Abnormal vitamin D status not only impacts the blood-retinal barrier but can also directly impair the structure and function of the retinal microvascular system. “This finding suggests that vitamin D may exert a systemic protective effect on retinal microvascular health, a mechanism closely linked to its anti-inflammatory and vascular endothelial protective functions,” the authors explained in their paper.Calcium metabolism abnormalities represent another crucial link connecting vitamin D status with retinal diseases. Vitamin D deficiency can lead to reduced intestinal calcium absorption and secondary hyperparathyroidism, increasing the risk of ectopic calcification in soft tissues. “In the eye, this imbalance in calcium‑phosphorus homeostasis may promote abnormal deposition of calcium salts, such as hydroxyapatite—in Bruch’s membrane—thereby accelerating its aging and functional decline and creating favorable conditions for the development of dry AMD,” the researchers wrote. “Moreover, recent research indicates that higher calcium levels are associated with a reduced overall risk of AMD, further strengthening the link between calcium homeostasis and AMD.”Another biological mechanism is overactivation of the complement system. Notably, vitamin D plays an important role in modulation. “Studies have shown that vitamin D deficiency can lead to abnormal expression of complement factors such as Factor B and C9, suggesting that its deficiency may exacerbate aberrant complement activation,” the authors wrote in their paper. “Therefore, in conditions of osteoporosis accompanied by vitamin D deficiency, complement-mediated chronic retinal damage may be amplified, further promoting the progression of AMD.”Matrix metalloproteinases (MMP), particularly MMP-9, may also serve as a key mediating factor. Studies have shown that MMP-9 not only plays a significant role in bone resorption in osteoporosis patients, but its serum levels are also markedly elevated in AMD patients. “MMP-9 degrades extracellular matrix, disrupting bone matrix in skeletal tissue and potentially compromising the structural integrity of Bruch's membrane in the eye, thereby promoting drusen formation and the progression of dry AMD,” the authors explained in their paper.The sex-specific disparity may be attributed to the pivotal role of estrogen. In women, estrogen not only maintains bone density by enhancing calcium absorption during bone remodeling but also exerts protective effects against AMD progression. “A systematic review by Kaarniranta et al. indicated that estrogen can delay retinal pigment epithelial cell senescence through receptor-mediated antioxidant pathways, such as modulating SIRT1 expression, thereby reducing drusen deposition,” the authors wrote. “Consequently, the sharp decline in estrogen levels following menopause simultaneously weakens protective mechanisms in both bone and retinal tissues, leading to the strong association between osteoporosis and AMD observed in women.”These findings highlight the importance of considering patients with osteoporosis—especially elderly women—as a potential high-risk group for dry AMD. Early retinal fundus screening in this population may contribute to improved disease management and prognosis.Click here for the journal source. Lin H, Sun X, Liu J, Chang Z. Exploring the casual relationship between osteoporosis and age-related macular degeneration: evidence from observation studies and mendelian randomization. Experimental Gerontology. February 6, 2026. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.