Calcium, vitamin D and involutional osteoporosis Roger M. Francis

Purpose of review Previous studies suggest that combined calcium and vitamin D supplementation decreases the risk of fractures in older people, particularly those living in care homes, but trials of vitamin D alone in fracture prevention have generated inconsistent results. This review examines the physiological functions of calcium and vitamin D, and the contrasting views of what constitutes an adequate dietary calcium intake and vitamin D sufficiency in adults, and highlights the results of recent large studies of calcium and vitamin D supplementation. Recent findings The RECORD study shows that calcium (1000 mg/day) and vitamin D (800 IU/day), either alone or in combination, are ineffective in the secondary prevention of osteoporotic fractures in older men and women living in the community. The Northern and Yorkshire Study also suggests that calcium (1000 mg/day) and vitamin D (800 IU/day) are of no benefit in the primary prevention of fractures in community-dwelling older women. Furthermore, the Wessex study demonstrated no reduction in fractures in older people living in the community treated with annual IM injections of vitamin D (300 000 IU). Summary The latest studies highlight that vitamin D, either alone or in combination with calcium supplementation, is ineffective in the primary or secondary prevention of fractures in community-dwelling older people. In contrast, calcium and vitamin D supplementation prevents fractures in institutionalized elderly people, who commonly have vitamin D deficiency and secondary hyperparathyroidism. Keywords calcium, fractures, older people, vitamin D, vitamin D deficiency Curr Opin Clin Nutr Metab Care 9:13–17. ß 2006 Lippincott Williams & Wilkins. University of Newcastle upon Tyne, Musculoskeletal Unit, Freeman Hospital, Newcastle upon Tyne, UK Correspondence to Professor R.M. Francis, Consultant Physician, Musculoskeletal Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK Tel: +044 191 223 1160; fax: +044 191 223 1161; e-mail: [email protected] Current Opinion in Clinical Nutrition and Metabolic Care 2006, 9:13–17

Abbreviations CI 1,25(OH)2D 25OHD RNI RR

confidence interval 1,25-dihydroxyvitamin D 25 hydroxyvitamin D reference nutrient intake relative risk

ß 2006 Lippincott Williams & Wilkins 1363-1950

Introduction Osteoporosis has been defined as a skeletal disorder characterized by compromised bone strength, predisposing a person to an increased risk of fracture [1]. The three major osteoporotic fractures are those of the forearm, vertebra and hip, but fractures of the humerus, clavicle pelvis and ribs are also common. The incidence of these fractures rises steeply with age, such that most occur in people above the age of 65 years, when they are associated with excess mortality, substantial morbidity and health and social service expenditure [2]. This paper examines the role that calcium and vitamin D play in the pathogenesis and management of involutional osteoporosis and in the prevention of osteoporotic fractures in older people.

Functions of calcium and vitamin D Calcium is required for a number of functions in the body including neuromuscular activity, membrane function, hormone secretion, enzyme activity, coagulation of the blood and skeletal mineralization. Over 99% of the body’s calcium is stored in bone, where it provides mechanical strength to the skeleton and serves as a mineral reservoir which can be drawn upon to maintain a normal plasma calcium. An adequate dietary calcium is required to offset the obligatory loss of calcium in the urine and digestive juices and prevent unnecessary loss of calcium from the skeletal reservoir [3]. Vitamin D is required not only for bone development and growth in children, but also for the maintenance of bone health in adults. The hormonally active metabolite of vitamin D is 1,25-dihydroxyvitamin D (1,25(OH)2D), which regulates calcium absorption from the bowel, mediates the mineralization of osteoid tissue within bone and plays an important role in muscle function. The major source of vitamin D is the skin, following exposure to ultraviolet radiation. The diet provides much smaller amounts although this source is essential when cutaneous 13

14 Ageing: biology and nutrition

production is limited because of lack of exposure to sunlight [3].

Dietary calcium requirements The recommended dietary calcium intake varies widely from country to country [4]. In the USA an intake of between 1000 and 1500 mg daily is recommended for adults, depending on age, gender and menstrual status [5]. In contrast, the reference nutrient intake (RNI) for calcium in the UK is 700 mg/day for an adult [4]. This value is two standard deviations above the estimated average requirement (EAR) of 550 mg/day, calculated from the efficiency of calcium absorption and the obligatory losses of calcium in the urine, digestive juices and sweat. The RNI should therefore provide sufficient calcium for 97.5% of the adult population, but higher intakes may be necessary in patients with osteoporosis [4]. The UK National Diet and Nutrition Survey shows a mean calcium intake of 704 mg/day in women aged 65–74 years, 680 mg/day between the ages of 75 and 84 years and 647 mg/day at or above the age of 85 years and above [6]. Over half of older women therefore have a dietary calcium intake below the RNI.

Vitamin D requirements As the major source of vitamin D is from cutaneous production after ultraviolet irradiation, there is no recommended dietary intake for vitamin D for adults in the UK up to the age of 65 years, except for those with reduced exposure to sunlight [4]. The RNI for vitamin D in these subjects and in people above the age of 65 years is 400 IU daily. An alternative approach is to define vitamin D sufficiency and deficiency in terms of circulating 25 hydroxyvitamin D (25OHD) concentration. As serum 25OHD is inversely related to parathyroid hormone, the 25OHD concentration below which parathyroid hormone increases is often used to identify the threshold of vitamin D insufficiency or deficiency. Lips [7] has classified vitamin D deficiency into mild (serum 25OHD 25–50 nmol/l), moderate (12.5–25 nmol/l) or severe (