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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 -
Osteoporosis and Sarcopenia Dec 2023Hypophosphatasia (HPP), also called Rathbun disease, is a rare genetic disorder that is caused by the loss-of-function mutation in the gene encoding tissue non-specific... (Review)
Review
Hypophosphatasia (HPP), also called Rathbun disease, is a rare genetic disorder that is caused by the loss-of-function mutation in the gene encoding tissue non-specific alkaline phosphatase. Doctor Rathbun first described the case of a 3-week-old infant who presented with severe osteopenia, rickets, and multiple radiographic fractures, and died shortly after of epileptic seizure and respiratory distress. The term "hypophosphatasia" was coined as the patients' alkaline phosphatase levels were significantly low. Since then, our understanding of HPP has evolved, and now we appreciate causative genetic mutation and the broad spectrum of clinical presentation depending on the age of onset, severity, and skeletal involvement: perinatal, infantile, childhood, adult and odontohypophosphatasia. The new development of enzyme replacement with asfostase alfa has saved the lives of severe form of hypophosphatasia. However, it is still unclear and remains challenging how to manage adult HPP that often presents with mild and non-specific symptoms such as muscle pain, joint stiffness, fatigue, anxiety, or low bone mass, which are common in the general population and not necessarily attributed to HPP. In this review, we will present 3 unique cases of adult HPP and discuss the pathophysiology, clinical presentation particularly neuromuscular and neurocognitive symptoms and management of adult HPP.
PubMed: 38374822
DOI: 10.1016/j.afos.2023.12.003