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BMJ (Clinical Research Ed.) Jun 2023To investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events.
DESIGN
Randomised, double blind, placebo controlled trial of monthly vitamin D (the D-Health Trial). Computer generated permuted block randomisation was used to allocate treatments.
SETTING
Australia from 2014 to 2020.
PARTICIPANTS
21 315 participants aged 60-84 years at enrolment. Exclusion criteria were self-reported hypercalcaemia, hyperparathyroidism, kidney stones, osteomalacia, sarcoidosis, taking >500 IU/day supplemental vitamin D, or unable to give consent because of language or cognitive impairment.
INTERVENTION
60 000 IU/month vitamin D (n=10 662) or placebo (n=10 653) taken orally for up to five years. 16 882 participants completed the intervention period: placebo 8270 (77.6%); vitamin D 8552 (80.2%).
MAIN OUTCOME MEASURES
The main outcome for this analysis was the occurrence of a major cardiovascular event, including myocardial infarction, stroke, and coronary revascularisation, determined through linkage with administrative datasets. Each event was analysed separately as secondary outcomes. Flexible parametric survival models were used to estimate hazard ratios and 95% confidence intervals.
RESULTS
21 302 people were included in the analysis. The median intervention period was five years. 1336 participants experienced a major cardiovascular event (placebo 699 (6.6%); vitamin D 637 (6.0%)). The rate of major cardiovascular events was lower in the vitamin D group than in the placebo group (hazard ratio 0.91, 95% confidence interval 0.81 to 1.01), especially among those who were taking cardiovascular drugs at baseline (0.84, 0.74 to 0.97; P for interaction=0.12), although the P value for interaction was not significant (<0.05). Overall, the difference in standardised cause specific cumulative incidence at five years was -5.8 events per 1000 participants (95% confidence interval -12.2 to 0.5 per 1000 participants), resulting in a number needed to treat to avoid one major cardiovascular event of 172. The rate of myocardial infarction (hazard ratio 0.81, 95% confidence interval 0.67 to 0.98) and coronary revascularisation (0.89, 0.78 to 1.01) was lower in the vitamin D group, but there was no difference in the rate of stroke (0.99, 0.80 to 1.23).
CONCLUSIONS
Vitamin D supplementation might reduce the incidence of major cardiovascular events, although the absolute risk difference was small and the confidence interval was consistent with a null finding. These findings could prompt further evaluation of the role of vitamin D supplementation, particularly in people taking drugs for prevention or treatment of cardiovascular disease.
TRIAL REGISTRATION
ACTRN12613000743763.
Topics: Humans; Aged; Vitamins; Cardiovascular Agents; Vitamin D; Myocardial Infarction; Dietary Supplements
PubMed: 37380191
DOI: 10.1136/bmj-2023-075230 -
Cureus Feb 2024Tumor-induced osteomalacia (TIO) is a rare complication of certain tumors involving the skeletal bones, mainly in the lower extremities and rarely the spine, that can...
Tumor-induced osteomalacia (TIO) is a rare complication of certain tumors involving the skeletal bones, mainly in the lower extremities and rarely the spine, that can cause skeletal abnormalities, osteopenia, and osteoporosis. The etiology of these tumors is unknown, and they are considered benign tumors that usually localize in bone or soft tissue anywhere in the body. Symptoms are nonspecific and vague, which causes a delay in diagnosis. These tumors produce fibroblast growth factor-23, which causes hypophosphatemia due to renal wasting of phosphate and inhibits vitamin D3 activation, resulting in osteomalacia. The majority of these tumors are osteoblastic and rarely osteolytic. A PET scan can detect the location and diagnose these tumors. Surgical resection, when feasible, is the treatment of choice and can lead to improvement, resolution of symptoms, and correction of hypophosphatemia. Patients usually present with a wide variety of nonspecific complaints. This case report presents an unusual presentation of TIO from a phosphaturic mesenchymal tumor involving the left acetabulum.
PubMed: 38389570
DOI: 10.7759/cureus.54712 -
Bone Reports Jun 2024Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast... (Review)
Review
INTRODUCTION
Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor.
MATERIAL AND METHODS
We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online.
RESULTS
We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively.
CONCLUSION
TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.
PubMed: 38774264
DOI: 10.1016/j.bonr.2024.101772 -
JCI Insight Dec 2023Fibroblast growth factor 23 (FGF23) is a phosphate-regulating (Pi-regulating) hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23...
Fibroblast growth factor 23 (FGF23) is a phosphate-regulating (Pi-regulating) hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23 excess, impaired skeletal growth, and osteomalacia. Blocking FGF23 became an effective therapeutic strategy in X-linked hypophosphatemia, but testing remains limited in autosomal recessive hypophosphatemic rickets (ARHR). This study investigates the effects of Pi repletion and bone-specific deletion of Fgf23 on bone and mineral metabolism in the dentin matrix protein 1-knockout (Dmp1KO) mouse model of ARHR. At 12 weeks, Dmp1KO mice showed increased serum FGF23 and parathyroid hormone levels, hypophosphatemia, impaired growth, rickets, and osteomalacia. Six weeks of dietary Pi supplementation exacerbated FGF23 production, hyperparathyroidism, renal Pi excretion, and osteomalacia. In contrast, osteocyte-specific deletion of Fgf23 resulted in a partial correction of FGF23 excess, which was sufficient to fully restore serum Pi levels but only partially corrected the bone phenotype. In vitro, we show that FGF23 directly impaired osteoprogenitors' differentiation and that DMP1 deficiency contributed to impaired mineralization independent of FGF23 or Pi levels. In conclusion, FGF23-induced hypophosphatemia is only partially responsible for the bone defects observed in Dmp1KO mice. Our data suggest that combined DMP1 repletion and FGF23 blockade could effectively correct ARHR-associated mineral and bone disorders.
Topics: Animals; Mice; Calcification, Physiologic; Extracellular Matrix Proteins; Familial Hypophosphatemic Rickets; Fibroblast Growth Factors; Hypophosphatemia; Mice, Knockout; Minerals; Osteomalacia
PubMed: 37943605
DOI: 10.1172/jci.insight.156850