Excessive Dietary Intake of Vitamin A Is Associated with Reduced Bone Mineral Density and Increased Risk for Hip Fracture

Melhus, Håkan; Michaëlsson, Karl; Kindmark, Andreas; Bergström, Reinhold; Holmberg, Lars; Mallmin, Hans; Wolk, Alicja; Ljunghall, Sverker

doi:10.7326/0003-4819-129-10-199811150-00003

Cited by 342 publications

(237 citation statements)

References 35 publications

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“…Addition of 9cRA to 1,25D treatment completely prevented the weight loss and kidney calcification seen with 1,25D treatment alone, without decreasing the effectiveness of 1,25D treatment against lung tumor incidence and multiplicity. An effect of retinoids on calcium homeostasis has been shown more clearly in studies investigating the association between vitamin A and fracture risk, [45][46][47][48] and the influence of retinoids on vitamin D regulation of serum calcium and bone mineral homeostasis. 35,49,50 Unfortunately, we were unable to obtain sufficient data to report serum or urine calcium levels in our study.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Mernitz

Smith

Wood

et al. 2007

Intl Journal of Cancer

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9-cis-Retinoic acid (9cRA) and 1a, 25-dihydroxyvitamin D 3 (1,25D) show promise as potential chemopreventive agents. We examined 9cRA and 1,25D, alone and in combination, for their potential to inhibit carcinogen (NNK)-induced lung carcinogenesis in A/J mice. A/J mice (n 5 14/group) were treated with 9cRA (7.5, 15, or 30 mg/kg diet), 1,25D (2.5 or 5.0 lg/kg diet), or a combination of 9cRA (15 mg/kg diet) plus 1,25D (2.5 lg/kg diet) for 3 weeks before and 17 weeks after carcinogen injection. Lung tumor incidence, tumor multiplicity, plasma 1,25D levels and kidney expression of vitamin D 24-hydroxylase (CYP24) were determined. Compared to carcinogen-injected controls, mice receiving 9cRA supplementation had significantly lower tumor multiplicity at all doses (decreased 68-85%), with body weight loss at the higher doses of 9cRA. Mice receiving 1,25D supplementation had significantly lower tumor incidence (decreased 36 and 82%) and tumor multiplicity (decreased 85 and 98%), but experienced significant body weight loss, kidney calcium deposition, elevated kidney CYP24 expression and decreased fasting plasma 1,25D levels. Although, there was no apparent influence on chemopreventive efficacy, addition of 9cRA to 1,25D treatment effectively prevented the weight loss and kidney calcification associated with 1,25D treatment alone. These data demonstrate that 9cRA and 1,25D, alone or combined, can inhibit lung tumor promotion in the A/J mouse model. Combining 1,25D with 9cRA has the potential to mitigate the toxicity of 1,25D, while preserving the significant effect of 1,25D treatment against lung carcinogenesis. The underlying mechanism behind this effect does not appear to be related to retinoid modulation of vitamin D catabolism. ' 2006 Wiley-Liss, Inc.Key words: lung cancer; 9-cis retinoic acid; 1a,25-dihydroxyvitamin D 3Chemoprevention by diet or drug intervention may offer a realistic and practical means of modifying the risk of lung cancer, the leading cause of cancer deaths in both men and women in the United States. 1 Two classes of chemopreventive compounds that have been considered are the retinoids and the active form of vitamin D, 1a,25-dihydroxyvitamin D 3 (1,25D, also calcitriol).Retinoids are required for proper differentiation of lung and upper airway epithelium, 2 and both 9-cis retinoic acid (9cRA, also 9-cis tretinoin) and all-trans retinoic acid have been shown to inhibit cell growth and proliferation in lung cancer cell lines. 3 Studies in animal models of lung cancer suggest that retinoids may be effective in cancer chemoprevention in vivo, but results have varied with species, dose and timing of treatment in relation to induction of carcinogenesis. [4][5][6] In human lung cancer, epidemiological evidence supports a role for vitamin A-rich foods and supplements in protection against the development of lung cancer in smokers and nonsmokers alike 7 ; however, clinical trials assessing the efficacy of retinoid supplementation against lung cancer have yielded inconsistent and inconclusive results. [8][...

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Section: Discussionmentioning

confidence: 99%

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Mernitz

Smith

Wood

et al. 2007

Intl Journal of Cancer

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“…Melhus and cols. (30) showed that excessive vitamin A supply associates negatively with BMD, even after adjustments in the other risk factors for osteoporosis. Experimental studies showed that vitamin A deficiency Arch Endocrinol Metab.…”

Section: Discussionmentioning

confidence: 99%

Bone mineral density in short bowel syndrome: correlation with BMI and serum vitamins C, E and K

Braga

Bizari

Suen

et al. 2015

Arch. Endocrinol. Metab.

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Objective: Bone loss has been established as a major extra-intestinal complication of short bowel syndrome (SBS). The purpose of this study was to correlate bone mineral density (BMD) with body mass index (BMI), serum vitamin and mineral levels in patients with SBS. Material and methods: The study was conducted on 13 patients (8 male and 5 female, 54.7 ± 11.4 years) with SBS (residual small bowel length of 10 to 100 cm). We determined the food ingestion, anthropometry, serum levels of vitamins C, A, D, E and K, as well as serum and urinary levels of phosphorus and calcium. BMD was measured by dual-energy x-ray absorptiometry (DXA). Results: Osteopenia and osteoporosis was diagnosed in all but one SBS patient. Serum levels of vitamin D were low in all volunteers. Sixty-one percent of patients had vitamin E deficiency; hypovitaminosis A and C occurred in one subject. BMI and C, E and K vitamin serum levels correlated with T-score of BMD. Conclusions: Osteopenia and osteoporosis were common in SBS patients. There was a correlation between BMD and the serum levels of vitamins C, E and K, an indicative that such vitamins may influence bone health. Arch Endocrinol Metab. 2015;59(3):252-8

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“…For example, chemotherapy, corticosteroids and retinoids received during induction and salvage therapy can decrease bone mineral density. [10][11][12][13] Furthermore, multiple myeloma is associated with systemic osteoporosis as a result of increased osteoclastic activity. 14 ABMT patients also may have general risk factors for osteoporosis that include older age, 15 thin body habitus, 16,17 a family history of osteoporosis, 18 smoking, 19,20 and physical inactivity.…”

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confidence: 99%

Decreased bone mineral density is common after autologous blood or marrow transplantation

Schimmer

Mah

Bordeleau

et al. 2001

Bone Marrow Transplant

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Summary:Survivors of autologous blood or marrow transplantation (ABMT) are predisposed to decreased bone mineral density (BMD), but data are lacking on the incidence and risk factors for this condition. Therefore, we measured BMD in 64 of 68 consecutive ABMT survivors (35 men and 29 women) attending the University of Toronto ABMT long-term follow-up clinic. Patients were evaluated a median of 4.2 years (range: 4.9 months-11.4 years) after ABMT. Median age at evaluation was 49.6 years (range: 23.5-68.2 years). At the L1-L4 vertebrae, 17 (26%) patients (eight men and nine women) had osteopenia and one male (2%) had osteoporosis. Mean BMD at L1-L4 did not differ from healthy young adults or age and sex matched controls. At the femoral neck, 30 patients (46%) (18 men and 12 women) had osteopenia and five (8%) (two men and three women) had osteoporosis. Mean BMD at the femoral neck was significantly lower than in healthy young adults and age-and sex-matched controls. By regression analysis, patients with decreased BMD were older than those with normal BMD (P = 0.02). Gender, body mass index, time from BMT to evaluation and presence of hypogonadism were not associated with decreased BMD. Treatment of decreased bone density was instituted and follow-up data were obtained 1 year after treatment in 22 of 39 patients with reduced BMD. Nineteen (86%) patients had stabilization or improvement of their bone density at follow-up. We conclude that, after ABMT, over half of the patients have evidence of osteopenia or osteoporosis. Men and women were equally affected. In our study, only older age at evaluation was predictive for loss of BMD. We recommend the measurement of BMD as an integral component to the follow-up of ABMT patients. Bone Marrow Transplantation (2001) As the number of long-term survivors of autologous blood or marrow transplantation (ABMT) increases, greater attention is turning to the late complications of this procedure. One such complication is decreased bone mineral densityosteopenia and osteoporosis. Osteopenia is a systemic condition characterized by reduced bone mass and increased susceptibility to bone fracture. Osteoporosis is a more severe reduction in bone mass and a greater susceptibility to bone fracture.In the short term, osteoporosis seems trivial compared with a diagnosis of cancer, but for those cured of their disease, decreased bone mineral density contributes to chronic morbidity and mortality in the form of bone fractures. For example, 50% of patients who sustain an osteoporosisrelated hip fracture require assistance with activities of daily living 1 and elderly patients who suffer an osteoporosis-related hip fracture have an increased 1-year mortality of 12-37%. 2 ABMT predisposes to decreased BMD through early and late acting mechanisms. ABMT is associated with an acute increase in bone turnover due to the high-dose chemotherapy, marrow reinfusion and G-CSF administration, but effects on long-term bone density are unknown. [3][4][5] The late effects of ABMT on BMD are primarily due to t...

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Excessive Dietary Intake of Vitamin A Is Associated with Reduced Bone Mineral Density and Increased Risk for Hip Fracture

Abstract: High dietary intake of retinol seems to be associated with osteoporosis.

Cited by 342 publications

References 35 publications

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Bone mineral density in short bowel syndrome: correlation with BMI and serum vitamins C, E and K

Decreased bone mineral density is common after autologous blood or marrow transplantation

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Excessive Dietary Intake of Vitamin A Is Associated with Reduced Bone Mineral Density and Increased Risk for Hip Fracture

Abstract: High dietary intake of retinol seems to be associated with osteoporosis.

Cited by 342 publications

References 35 publications

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D3 and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D3 and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Bone mineral density in short bowel syndrome: correlation with BMI and serum vitamins C, E and K

Decreased bone mineral density is common after autologous blood or marrow transplantation

Contact Info

Product

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Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity