High-Dose Vitamin D Supplementation Adverse Effects & Sex Differences

With vitamin D supplementation widely administered to postmenopausal females for osteoporosis prevention, researchers examined whether the dose-response relationship with high-dose vitamin D supplementation for bone density and strength differed between males and females. For the study, patients aged 55 to 70 were randomized to 400 IU, 4,000 IU, or 10,000 IU daily vitamin D3 and scanned with high resolution peripheral quantitative CT to measure total volumetric BMD (TtBMD) at baseline and 6, 12, 24, and 36 months. When compared with 400 IU, treatment with 4,000 IU or 10,000 IU resulted in TtBMD losses in females but not in males. At 36 months, females lost 1.8% on 400 IU, 3.8% on 4,000 IU, and 5.5% on 10,000 IU at the radius, whereas males lost 0.9%, 1.3%, and 1.9%, respectively. TtBMD losses at the tibia were smaller but followed the same trend. No significant bone strength interactions were observed. “Our findings do not support a benefit of high-dose vitamin D supplementation for bone health, and raise the possibility of harm for females,” write the study authors.

T1D Linked With Bone & Muscle Deficiencies in Children & Adolescents

Recent data suggest that type 1 diabetes (T1D) compromises muscle mitochondrial oxidative capacity, potentially impeding skeletal development beyond the already understood impairment of bone formation. With state-of-the-art high resolution peripheral quantitative CT (HRpQCT) providing 3D measures of cortical and trabecular volumetric BMD, microarchitecture, and micro-finite element estimates of bone strength that correlate with fractures in children and adults, study investigators obtained HRpQCT scans in patients with T1D aged 10-18 with at least 3 years since their diagnosis and healthy controls. Failure load, regional lean mass, leg strength, arm strength, and insulin-like growth factor 1 (IGF-1) were also assessed, with all bone and muscle measures converted to sex-specific Z-scores relative to age, based on data in the healthy controls. In males, T1D was associated with significant deficits in muscle strength that were not explained by lower IGF-1 Z-scores or lower muscle mass when compared with controls. Males with T1D also had significantly lower bone failure load in the tibia, but not the radius, compared with controls, with these deficits persisting despite adjustment for lower IGF-1 levels and muscle mass, suggesting a direct effect of T1D on bone. In females with T1D, BMI Z-scores were significantly greater than those of controls and males with T1D. Both with and without adjustment for BMI, significant deficits in muscle mass and strength were not observed in females with T1D when compared with controls. When compared with female controls, those with T1D had significantly lower failure load in the tibia diaphysis upon adjustment for BMI.

Low Vitamin D Predicts ICU Admission, Poor Survival in COVID-19

Data indicate that COVID-19-related mortality rates are particularly high in countries with lower average levels of vitamin D or UVB radiation exposure, including Italy. To examine the relationship between vitamin D levels and COVID-19 severity and associated mortality, researchers studied 103 symptomatic patients with COVID-19 with respiratory insufficiency who were admitted to a Milan hospital from March 9 to April 30, 52 patients with mild COVID-19 who were recruited from a nearby nursing home, and 206 healthy controls who were matched 2:1 with symptomatic patients of the same age, weight, and gender, from 3,174 patients who had vitamin D measured during a routine check-up from January to March 2020. Patients in the hospitalized group had lower mean vitamin D levels (18.2 ng/mL) than those with mild COVID-19 (30.3 ng/mL) or those in the control group (25.4 ng/mL). Patients with symptomatic versus mild COVID-19 were less likely to be taking a vitamin D supplement at baseline (30% vs 79%). Among symptomatic patients, mean vitamin D levels were inversely associated with interleukin-6 and C-reactive protein, direct expressions of inflammatory status. Patients with severe COVID-19 who were admitted to the ICU, as opposed to a ward, had lower mean vitamin D levels (14.4 vs 22.4 ng/ mL) and were more likely to have vitamin D deficiency (vitamin D < 20 ng/mL; 80% vs 45%). Patients admitted to the ICU who died had lower baseline vitamin D levels than those who survived (13.2 vs 19.3 ng/mL). Vitamin D levels were inversely associated with respiratory distress requiring ICU admission [odds ratio (OR), 1.06] and with mortality (OR, 1.18), independent of IL-6 levels and other comorbidities.

Specialized Osteological Care Addresses Poor Treatment Adherence

Although evidence indicates the availability of good therapy options for patients with osteoporosis, research shows significant deficits in outpatient care and poor adherence levels, with studies suggesting only one-third of patients with osteoporosis remain on therapy after 2 years. To investigate whether specialized osteoporosis management improves adherence with medications when compared with standard care, researchers assessed data on patients with osteoporosis who initiated medication between January and June 2017 following at least 12 months of no medication use and received either standard care or specialized osteoporosis management provided by an osteologist. At 2 years, only 33.46% of patients receiving standard management remained on their osteoporosis therapy, compared with 92.70% of those who received specialized management. “Specialized management of patients by an osteologist provides a key ingredient to deliver effective osteoporosis treatment,” write the study authors. “This has the potential to improve treatment persistence, slow disease progression, and prevent fractures, thereby reducing costs and improving quality of life.”

Fall & Fracture Risk Reduced With Increased Dairy in Frail Elderly

While studies have shown fracture risk reductions in older residents of special living facilities with calcium plus vitamin D supplements, whether it’s best to obtain adequate intake of both via supplements, overall healthy diet, or extra dairy intake remains unclear. To shed some light on this, study investigators randomized 60 “old-age institutions” in Australia to provide residents with usual menus or an altered menu that increased dairy consumption from 2 to 3.5 servings per day for 2 years. Residents in both groups had similar characteristics, including a mean age of 87, 68% female makeup, and baseline vitamin D levels (72 nmol/L) and bone morphology. Daily calcium and protein intakes remained at 650 mg and 59 g, respectively, for the control group but increased to >1,100 mg and 72 g, respectively, in the intervention group. At 2 years, the increased daily intake was associated with an 11% reduction in falls (62% vs 57%), a 33% reduction in fractures (5.2% vs 3.7%), a 46% reduction in hip fractures (2.4% vs 1.3%), no difference in mortality (28% in both groups), a slowing in bone loss, and an increase in insulin-like growth factor-1.