F. Scopacasa

A longitudinal study of bone-related biochemical changes at the menopause

objective  To evaluate the effects of the menopause on bone‐related biochemical variables in a longitudinal study.

Vitamin D receptor genotypes are related to bone size and bone density in men

Three restriction fragment length polymorphisms in the vitamin D receptor gene have been associated with a low bone density in twin and female population studies, but no studies have been conducted exclusively in men. We studied 146 normal men aged 20–83 years. Bone density was measured in the spine, hip, whole body and forearm, and the Bsm polymorphism for the vitamin D receptor was detected by the polymerase chain reaction. Men with genotype BB tended to have a lower bone density at all but one site than the other genotypes. In the men ≤50 years of age bone density in the forearm was 7% lower in the BB than the Bb and bb groups (P  =  0.030) but bone mineral content did not differ between the groups. Bone area was greater in the BB genotype at all sites. This was statistically significant in the forearm (P  =  0.026). We conclude that BB genotype is associated with lower bone density in men, which may be due to larger bone size rather than reduced bone mass.

The relation between bone density, free androgen index, and estradiol in men 60 to 70 years old.

The cause of age-related bone loss in men is poorly understood. Previous studies of the relationship between bone density and serum androgens have yielded inconsistent results, perhaps partly because age is a determinant of both. Recent studies suggest that serum estrogen levels influence bone density in adult men. In order to determine whether bone mineral density (BMD) and bone turnover are associated with serum sex steroids, we investigated 37 normal men within a narrow age range (60-70 years). Bone mineral density at the forearm, hip, and spine, testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI:T/SHBG), estradiol (E), free estradiol index (FEI:E/SHBG), and markers of bone formation (alkaline phosphatase, osteocalcin, procollagen type I C-terminal extension peptide) and bone resorption (hydroxyproline/creatinine [OHPr/Cr], deoxypyridinoline/creatinine [Dpd/Cr], pyridinoline/creatinine, collagen type I cross-linked telopeptide) were measured. Bone mineral density was positively related (r > 0.35, p < 0.05 at all sites) to log FAI, whereas there was no significant relationship between BMD and either serum total testosterone, serum E, or FEI. Bone density at the spine and hip were inversely related to both OHPr/Cr (r > -0.41, p < 0.05 for all sites) and Dpd/Cr (r > -0.36, p < 0.05 for all sites). OHPr/Cr (r = -0.41, p < 0.05) and Dpd/Cr (r = -0.41, p < 0.05) were both inversely related to log FAI. We conclude that BMD and bone turnover in adult men are related to plasma free androgens.

Intestinal calcium absorption in men with spinal osteoporosis

To investigate the role of serum 1,25‐dihydroxyvitamin D (1,25D) in the decreased calcium absorption found in men with osteoporosis.

Relation between calcium absorption and serum calcitriol in normal men: evidence for age-related intestinal resistance to calcitriol.

Objective: To obtain information on the causes of age-related bone loss in men and the concomitant decline in calcium absorption.Design: Cross-sectional study.Setting: Adelaide, South Australia, Australia.Subjects: A total of 95 healthy, Caucasian men (age range 27–87 y).Results: Calcium absorption declined with age (r=−0.46, P<0.0001), as did 24-h urine calcium, phosphate and creatinine (r>−0.21, P<0.05 for all); serum calcitriol and 25 hydroxyvitamin D did not change with age. Calcium absorption was related to serum calcitriol (r=0.20, P=0.05). An inverse relation between the residual deviations in calcium absorption, after allowing for its dependence on calcitriol, and age (F=5.4, P<0.005) was observed. The 24-h urinary calcium, phosphate and creatinine were all related to calcium absorption (r>0.41, P<0.0001). Forearm bone density fell with age (r=−0.45, P<0.0001) but was not related to calcium absorption, or markers of bone turnover.Conclusions: In healthy Caucasian males (i) calcium absorption falls, but serum calcitriol does not change with age, (ii) the relation between calcium absorption and serum calcitriol changes with age, indicative of an intestinal resistance to calcitriol and (iii) calcium absorption is a significant determinant of 24-h urinary calcium excretion.

Effect of perimenopause on calcium absorption: a longitudinal study

Objective Cross-sectional studies suggest that the rise in calcium requirement at the menopause may be attributable, at least in part, to a fall in intestinal calcium absorption. The aim of the present study was to determine the effect of the menopause on intestinal calcium absorption and the relationship between any change in calcium absorption and serum calcitriol. Methods Radiocalcium absorption and serum calcitriol were measured in 72 women aged 47.3 (standard error, SE 0.19) years who were initially premenopausal (as judged by menstrual history and serum follicle stimulating hormone (FSH)) and again 18 months later. Results Calcium absorption fell at the second visit from 0.72 (0.029)/h to 0.64 (0.029)/h (p = 0.003). Serum calcitriol had also fallen at the second visit from 124 (4.2) pmol/l to 111 (4.0) pmol/l (p = 0.007). At that visit, serum FSH exceeded the premenopausal reference range in 11 subjects and the menstrual cycle had become irregular in 24 of them. In the 11 women with raised FSH at the second visit, radiocalcium absorption fell from 0.85/h (0.097) at baseline to 0.57/h (0.049) (p = 0.008), but only from 0.70/h (0.028) to 0.65/h (0.033) (not significant) in the remaining 61. Similarly, radiocalcium absorption fell significantly (p = 0.003) in the 24 women with irregular menses, but not in the remaining 48 who continued to menstruate regularly. These changes in calcium absorption were still significant after correction for changes in calcitriol levels. Conclusion The perimenopause is associated with a fall in calcium absorption, which is only in part attributable to a fall in calcitriol levels.

Effect of physical activity on femoral bone density in men

Although most patients with osteoporosis are women, up to one third of hip fractures occur in men. There is little information about which factors influence bone density in men.1 Vigorous activity may lead to bone gain, while immobilisation causes bone loss. A sedentary lifestyle could, therefore, increase the risk of fractures.2 We therefore examined the relation between physical activity and bone density in normal men. One hundred and thirty seven healthy white men, comprising husbands of women attending our osteoporosis clinic, laboratory staff, and hospital workers who were enrolled in a normal bone study, listed their regular physical and sporting activities. Subjects taking drugs or with diseases likely to affect calcium metabolism were excluded. Forty eight were smokers (mean 15 cigarettes/day), and 120 drank alcohol (mean 8.6 g of alcohol/day). The time per week spent on each activity was …

Relationship between calcium absorption and plasma dehydroepiandrosterone sulphate (DHEAS) in healthy males

Context  Impaired gut sensitivity to 1,25‐dihydroxyvitamin D (1,25(OH)2D), leading to reduced intestinal calcium absorption, has been reported in older men and women. While this phenomenon in postmenopausal women has been attributed to oestrogen deficiency, it is unclear whether the same observation in older men correlates with the age‐related decline in androgen concentrations.

Inhibition of bone resorption by divided-dose calcium supplementation in early postmenopausal women.

Abstract. We have previously shown that a calcium (Ca) supplement of 1000 mg given in the evening reduces the overnight and early morning, but not the daytime, excretion of bone resorption markers in postmenopausal women within five years of the menopause. In the present study, we have looked at the effect of splitting the Ca into two doses of 500 mg each given in the morning and evening. We studied 19 healthy women (median age 53 years) who were all within 5 years of the menopause. On the 2 study days, urine was collected from 9 a.m. to 9 p.m. (day collection), and from 9 p.m. to 9 a.m. (night collection); a further fasting (spot) urine sample was obtained at 9 a.m. at the end of the night collection. The first day was a control day; on the second day the subjects ingested 500 mg Ca as the carbonate at 9 a.m. and 9 p.m. We measured pyridinoline cross-links excretion in all the samples, as well as hydroxyproline in the fasting urine. The Ca supplements lowered urinary excretion of the markers during the day (P < 0.01), had only a marginal effect during the night, but reduced excretion significantly in the fasting urine (P < 0.001). In the whole 24-hour period, the falls in resorption markers were small but comparable to those seen after the ingestion of 1 g of Ca in the evening. We conclude that the acute administration of 0.5 g Ca in the morning and evening reduced the markers of bone resorption in early postmenopausal women during the day but not during the following night, whereas the single 1 g supplement had the reverse effect. Over the 24-hour period, there was nothing to choose between the two regimes. Women at this stage in their life cycle probably require a larger Ca supplement if they are not taking estrogen.

The effects of low dose norethisterone on biochemical variables in postmenopausal women.

Abstract: Norethisterone 2.5 mg/day was administered to 26 postmenopausal women (aged 54–79 years) with varying degrees of osteoporosis and with a forearm bone mineral density value more than 2 SD below the young normal mean. Fasting blood and urine samples were collected and radiocalcium absorption measured at baseline and after treatment for a median period of 4 months. There were significant falls in serum calcium and its fractions, phosphate, alkaline phosphatase and cholesterol (HDL and LDL), and significant rises in serum chloride and parathyroid hormone. In the urine, there were significant falls in calcium, sodium and hydroxyproline. These changes were in close agreement with our previously reported responses to norethisterone 5 mg/day. We conclude that norethisterone in a dose of 2.5 mg/day is probably as effective as 5 mg/day in reducing bone resorption in postmenopausal women with low bone density.