Relationships between parathyroid hormone, 25-hydroxyvitamin D, and bone mineral density in elderly men

Age and Ageing,  May, 1993  by Sean Murphy,  Kay-Tee Khaw,  Ann Prentice,  Juliet E. Compston

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Introduction

Osteoporotic fractures are an important cause of morbidity and mortality in the elderly population [1]. Although the determinants of bone mass [2] and causes of osteoporosis in men [3, 4] have been less extensively studied than in women, fractures are also an important public health problem among men. In the United Kingdom, the probability that a man will suffer a fractured hip by age 85 years is 5% [5]. Age-specific incidence rates for hip fracture in men have increased 2-3-fold over the past few decades [6], though this increase may be reaching a plateau [7]. Even if 1985 age-specific incidence rates remain unchanged, there will be a 50% increase in the number of hip fractures in men by the year 2016 due to the ageing of the population [5].

Low bone mass is an important risk factor for fractures [8, 9]. Cross-sectional [10, 11] and longitudinal studies [12, 13] have demonstrated that men lose bone mass with increasing age. However, the pathophysiological basis for this age-associated bone loss is not clear. Increased bone resorption with ageing may in part be caused by impaired calcium and vitamin D homoeostasis with resultant secondary hyperparathyroidism (14, 15]. Calcium intake and absorptive efficiency decrease with age [16]. Calcitriol, the main determinant of calcium absorption, decreases in men after age 65 years [17], and this may be explained by an age-associated decrease in responsiveness of renal 1-alpha-hydroxylase to parathyroid hormone (PTH) [18]. Vitamin D stores also decline with ageing [19].

Little is known about the relationships between PTH, vitamin D status, and bone mass in elderly men [20]. In particular, there are no published data examining these relationships at the hip, the most relevant site clinically. In this paper we report on PTH, vitamin D status, and bone mineral density at the hip and spine among 133 healthy elderly men.

Methods

Subjects: Men aged 65-76 years living in the community were identified from general practice age-sex registers in Cambridge. Subjects were recruited by letter requesting participation in a health survey including a bone mineral density measurement. We report the results of a pilot study on 133 men, a response rate of approximately 50%, from two general practices. They were unselected for health status. Each subject completed a questionnaire describing health and lifestyle characteristics Weight and height were measured by trained observers and body mass index (BMI) was calculated as weight in kg/(height in metres)[2]. All subjects provided informed consent and the research protocol was approved by the hospital ethics committee.

Biochemical assays: During January to June 1991, a non-fasting blood sample was drawn from each subject between 09 h 00 and 15 h 00 and the serum was removed and stored at -70[degrees]C until assayed. Serum total 25-hydroxyvitamin D (25-hydroxycholecalciferol, D2 and 25-hydroxyergocalciferol, D3) was assayed in duplicate using a commercial kit (Incstar Inc., Stillwater, MN, USA). This involves an initial extraction procedure followed by an equilibrium radio-immunoassay. Inter- and intra-assay coefficients of variation were 6.5% and 16%, respectively. Serum intact parathyroid hormone (1-84, hPTH) was measured in duplicate with a commercial kit (N-tact PTH IRMA Kit, Incstar Inc., Stillwater, MN, USA) using a two-site immunoradiometric assay as described by Lindall et al. [21]. Inter- and intra-assay coefficients of variation were 6.7% and 4.5%, respectively. Serum calcium (corrected for albumin level), alkaline phosphates, and phosphate were measured in a routine biochemistry laboratory.

Bone mineral density measurements: Spine (L2-L4) and hip (neck, trochanter, intertrochanteric, and Ward's Triangle) bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry (DEXA) using the Horologic QDR-1000 (Horologic Inc., Waltham, MA, USA). Bone mineral density results were expressed in g/[cm.sup.2]. Precision for in vivo spine and hip site measurements (24 paired measurements in normal volunteers) was 1.0% and 1.5-3.0%, respectively [22].

Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, Ill, USA) on the mainframe computer at the University of Cambridge. Pearson and partial correlation coefficients were computed and two-sided statistical tests were used throughout. Mean age and body mass index adjusted levels of biochemical variables by tertiles of regional BMD were compared by analysis of variance.

Results

The baseline demographic, biochemical, and bone mineral density measurements are given in Table I. Twenty-seven of the 133 men (20.3% ) reported intake of vitamin supplements during the 6 months before entering the study; multivitamins (n = 10), calcium (n = 1) and fish oil (n = 17). One subject used both fish oil and multivitamins. There were no significant differences in any of the baseline variables between users and non-users of vitamin supplements, therefore both groups were combined.