Effect of Tamoxifen on Bone Mineral Density
Tamoxifen has different effects on bone mineral density depending on menopausal status: it increases bone mineral density in postmenopausal women but may cause bone loss in premenopausal women. 1
Effects in Postmenopausal Women
- Tamoxifen acts as an estrogen agonist on bone tissue in postmenopausal women with typically lower estrogen levels, resulting in increased bone mineral density 1
- In postmenopausal women with breast cancer, tamoxifen is associated with preservation of bone mineral density and reduced fracture risk 1
- Studies have shown that tamoxifen increases bone mineral density in the lumbar spine by approximately 0.61% per year in postmenopausal women, while those on placebo experienced a decrease of 1.00% per year 2
- The bone-preserving effect of tamoxifen in postmenopausal women is evident primarily in trabecular bone (spine) rather than cortical bone 3, 4
- Long-term studies (up to 7 years) have not shown accelerated bone loss with tamoxifen treatment in postmenopausal women 5
Effects in Premenopausal Women
- In premenopausal women, tamoxifen may oppose the more potent effects of estrogen on bone and potentially increase the risk for osteoporosis 1
- Tamoxifen taken for 3 years by premenopausal women has been associated with bone loss 1
- The FDA label notes that in a subgroup analysis of the P-1 trial, tamoxifen was associated with significant bone loss of the lumbar spine and hip in premenopausal women 6
- Despite the potential for bone loss, the National Comprehensive Cancer Network (NCCN) panel does not recommend monitoring of bone mineral density in premenopausal patients on tamoxifen, as development of osteopenia/osteoporosis in this population is considered unlikely 1
Mechanism of Action
- Bone is an estrogen-responsive tissue on which tamoxifen can act as either an estrogen agonist or antagonist, depending on the prevailing estrogen levels 1
- In postmenopausal women, tamoxifen decreases biochemical markers of bone turnover, including osteocalcin and alkaline phosphatase, suggesting reduced bone remodeling 3, 4
- These changes in serum concentration of biochemical markers reflect decreased bone turnover and contribute to the preservation of bone mineral density 3
Clinical Implications
- For postmenopausal women with breast cancer, tamoxifen provides a beneficial effect on bone health in addition to its anti-cancer properties 1
- For premenopausal women who develop chemotherapy-induced premature menopause, bisphosphonates may provide additional bone protection even when used concurrently with tamoxifen 1
- When comparing treatment options, tamoxifen has a more favorable effect on bone mineral density than aromatase inhibitors, which are associated with increased bone loss and fracture risk 1
- In the ATAC trial, anastrozole significantly increased fracture risk compared with tamoxifen (7.1% vs 4.1%) after a mean of 37 months follow-up 1
Comparison with Other SERMs
- Raloxifene, another selective estrogen receptor modulator (SERM), has also been shown to increase bone mineral density and reduce vertebral fracture risk in postmenopausal women 1
- In the STAR trial, there was no difference in the incidence of bone fracture between postmenopausal women taking either raloxifene or tamoxifen 1
- Unlike tamoxifen, raloxifene is FDA approved specifically for the prevention and treatment of osteoporosis in postmenopausal women 1
Monitoring and Management
- For postmenopausal women on tamoxifen, routine bone density monitoring is not necessary due to the bone-preserving effects 1
- For premenopausal women who develop chemotherapy-induced menopause while on tamoxifen, bisphosphonates may be considered as one of several potential options for preservation of bone density 1
- For women transitioning from tamoxifen to aromatase inhibitors, monitoring bone health becomes more important due to the increased risk of bone loss with aromatase inhibitors 1