Proof/Link?
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Here you go:
Influence of drugs on vitamin D and calcium metabolism
And here is the anti estrogen part specifically
Anti-Estrogens
The anti-estrogens include the following:
[filled square] aromatase inhibitors, such as anastrozole, letrozole, and exemestane,
[filled square] the estrogen receptor antagonist, fulvestrant and
[filled square] the selective estrogen receptor modulators, tamoxifen and toremifene.
All these active substances are used in the treatment of estrogen receptor-positive breast cancer. As aromatase inhibitors block estrogen synthesis and thus markedly reduce estrogen levels, treatment with these active substances also results in a severe reduction of the effect of estrogens on bone. Estrogens promote intestinal calcium absorption and bone mineralization; above all, however, they inhibit osteoclast activity. During aromatase inhibitor therapy, up to 50% of women report bone and muscle pain. Intake of aromatase inhibitors reduces bone density and increases the risk of bone fractures. Similar effects are likely following administration of a pure estrogen receptor antagonist; no data are yet available, however, on the long-term effect of fulvestrant on bones.42-44
Selective estrogen receptor modulators have estrogenic or anti-estrogenic effects, depending on the tissue. Whereas tamoxifen reduces the effects of estrogens in the breast, its effect on bone more closely resembles that of an estrogen receptor agonist and it shows a certain antiresorptive effect. Nevertheless, a decrease in bone density was observed in various studies during tamoxifen therapy, particularly in pre-menopausal women. Further side effects occurring in association with tamoxifen are bone and muscle pain and a rise in serum triglyceride levels.45-47
Aromatase inhibitor associated arthralgia limits adherence to therapy in breast cancer. The pathophysiology may involve vitamin D status. Vitamin D deficiency is associated with a syndrome of musculoskeletal symptoms with generalized nonspecific musculoskeletal pain and stiffness, as well as impaired muscle strength and function that is similar to that induced by aromatase inhibitors therapy.44 Hypovitaminosis D has been suggested as an underlying etiology in individuals with persistent, nonspecific musculoskeletal pain, comparable with the symptoms of osteomalacia.48 In addition to musculoskeletal symptoms, vitamin D deficiency has been implicated in accelerated bone loss in women with breast cancer receiving aromatase inhibitors therapy.49 A possible mechanism of AI-induced musculoskeletal symptoms and their improvement with vitamin D supplementation is that reduction in joint estrogen levels may unmask subclinical vitamin D deficiency. Estrogen increases activity of 1-α hydroxylase responsible for conversion of 25(OH)D to the biologically active 1,25(OH)2D.50,51 In addition estrogen increases expression of the Vitamin D receptor and VDR gene via activation of ERK 1/2 signaling pathway Increasing vitamin D substrate via higher doses may increase the active hormone 1,25-dihydroxyvitamin D with resultant reduction in joint symptoms.52,53
A prospective study with 290 women investigated the effect of vitamin D status on the occurrence of arthralgia during treatment with aromatase inhibitors, such as anastrozole, letrozole and exemestane.39 At baseline, 90% of the women had a calcidiol value < 30 ng/ml (75 nmol/L). Despite vitamin D supplementation with 800 IU daily and, depending on the baseline value, sometimes with an additional 16,000 IU every two weeks, adequate 25(OH)D levels were only achieved in half the women within a three-month period. During the course of the study, there was an increase in joint pain (mean 1.16 points SD 2.66; p < 0.001) and the increase was significantly (p = 0.02) attenuated in those that reached concentrations of 25(OH)D of ≥ 40 ng/ml, with a lower risk of incident arthralgia [OR 0.12 (0.03 to 0.40)]. A target concentration of 40 ng/ml 25(OH)D may prevent development of AI-induced arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline.54
In a pilot study the prevalence of suboptimal vitamin D status in 60 women initiating adjuvant therapy with letrozole for breast cancer was assessed, and determined, whether the supplementation of 50,000 IU vitamin D per week could reduce musculoskeletal symptoms and fatigue associated with aromatase inhibitors therapy. Baseline 25(OH)D levels were obtained, and women were started on letrozole. Four weeks later, women with baseline 25(OH)D levels ≤ 40 ng/mL were started on vitamin D supplementation of 50,000 IU per week. At week 16, after 12 weeks on high-dose vitamin D, 25(OH)D levels were measured. At baseline, 63% of women exhibited vitamin D deficiency [25(OH)D: < 20 ng/mL] or insufficiency [25(OH)D: 20–29 ng/mL]. 25(OH)D levels > 40 ng/mL were achieved in all 42 subjects who received for 12 weeks 50,000 IU vitamin D per week, with no adverse effects. Furthermore, the vitamin D therapy with 50,000 IU vitamin D/week resulted in clinically significant improvement in disability from joint symptoms.55,56 This early data on vitamin D supplementation under aromatase inhibitors therapy look promising, but results from larger clinical trials are needed.
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