The Use of Vitamins and Minerals in Skeletal Health

American Association of Clinical Endocrinologists and the American College of Endocrinology Position Statement

Daniel L. Hurley, MD, FACE; Neil Binkley, MD, FACE; Pauline M. Camacho, MD, FACE; Dima L. Diab, MD, FACE, FACP, CCD; Kurt A. Kennel, MD, FACE; Alan Malabanan, MD, FACE, CCD; Vin Tangpricha, MD, PhD, FACE


Endocr Pract. 2018;24(10):915-924. 

In This Article

Noncalcium Minerals

Approximately 85% of the body's phosphorus is found in bone. Phosphate is plentiful in most foods, particularly in processed foods and sodas. Phosphate homeostasis occurs primarily by renal phosphate excretion through the effects of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23)/Klotho. Phosphate is readily absorbed in the gut, enhanced to some extent by 1,25-dihydroxyvitamin D. Insufficient phosphate intake can lead to impaired bone mineralization and rickets or osteomalacia, although inadequate intake is rarely a concern, except for persons experiencing starvation. Data suggest increased dietary phosphate intake is associated with increased PTH and FGF-23 levels and increased bone resorption.[23] However, excessive phosphate consumption does not interfere with calcium absorption if there is adequate calcium intake[24] and does not seem to be associated with a lower BMD.[25] Inaccurate estimates of dietary phosphate intake, the association of inorganic acid load with dietary phosphate, and the presence of a circadian rhythm of serum phosphate are all factors that might affect nutrient studies of phosphate.[26] Phosphate supplementation in otherwise healthy adults is not recommended and may be detrimental to bone, particularly in those with compromised renal function or low calcium intake.

Magnesium, an intracellular cation and cofactor for multiple enzyme systems, is necessary for both calcium and potassium homeostasis. Although found widely in foods, 48% of the U.S. population consume less than the recommended daily amount (RDA) of magnesium.[27] Magnesium homeostasis is primarily regulated by the kidneys, and deficiency may occur from renal causes (diuretics, diuresis, tubular necrosis, etc.) or GI malabsorption. Hypomagnesemia may impair osteoblast function, decrease PTH and 1,25-dihydroxyvitamin D production or action, and increase osteoclast activation.[27] Effects of magnesium supplementation on BMD are variable. A Women's Health Initiative (WHI) study analysis by food questionnaire found hip and whole-body BMD significantly related to magnesium intake, although fracture risk was unchanged except in women at the highest quintiles of magnesium intake.[28] At present, there is no evidence to support routine magnesium supplementation in otherwise healthy adults.

Fluoride is naturally present in soil and water and consequently found in the food chain. Fluoride is absorbed completely in the GI tract. Fluoride absorption drops to 50 to 80% when complexes form with proteins, calcium, and other minerals. Approximately 95% of bodily fluoride is found in the bones and teeth, and fluoroapatite is antimicrobial and strengthens dental enamel. Fluoride stimulates bone formation at low doses, and although the mechanism is unclear, possible means include increasing osteoblast number and function.[29] At a dose of 75 mg/day, bone may become abnormally mineralized and susceptible to fracture,[30] and skeletal fluorosis has developed from excessive consumption of fluoride in tea.[31] Conversely, although 25 mg twice daily dosing of slow-release fluoride showed some success to increase BMD and reduce vertebral fractures,[32,33] a meta-analysis reported no benefit for reducing vertebral fractures and an increased nonvertebral fracture risk after 4 years of treatment.[34] Thus, although controversial, fluoride supplementation is not recommended for skeletal health.

Strontium is also a naturally occurring mineral in soil and water. Strontium has chemical similarity to calcium but is found primarily on the surface of bone apatite crystals, and only a small amount replaces calcium within the crystal lattice. Strontium results in a reduced calcium and increased carbonate content of the apatite crystal, thereby enlarging the crystal lattice size. Strontium is rapidly incorporated into bone and reduces bone resorption while modestly stimulating bone formation. Strontium increases BMD related to effects on bone turnover, but due to physicochemical consequences of replacing calcium within the lattice structure[35] may not improve bone strength. There is no evidence of bone toxicity or impaired mineralization at low doses, but strontium has induced osteomalacia in animals, and there may be increased susceptibility in persons with renal failure.[36] Strontium is approved outside the U.S. for the treatment of osteoporosis and reported to decrease the incidence of vertebral and nonvertebral fractures.[37,38] However, due to lack of data on bone health and concerns of severe cutaneous drug reactions and increased CV events, strontium supplementation is not recommended for skeletal health. Strontium ranelate is now restricted to severe osteoporosis treatment in Europe due to concerns about its cardiovascular adverse events. In addition, a drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) must be considered in anyone taking strontium ranelate who develops a rash and systemic symptoms, and the drug should be stopped and not recommended for future use.

Boron is a trace element found naturally in plants, and a diet consuming fruits, leafy vegetables, nuts, and legumes is high in boron. Boron does not seem to have a clear biochemical function in humans,[39] but it may have a role in reproductive and bone health in animals.[40] Boron may stabilize and extend the half-life of vitamin D and estrogen and increase the renal retention of calcium and magnesium, but there are insufficient data to recommend supplementation for skeletal health.[41]

Sodium intake increases urinary calcium excretion, thereby potentially increasing the risk for kidney stones and bone loss.[42,43] An association of sodium intake with decreased hip[44] or spine BMD[45] is reported, but an analysis of WHI data did not find any association between sodium intake and BMD or hip fracture risk independent of calcium intake.[46]