B. E. Christopher Nordin

Interim report and recommendations of the World Health Organization Task-Force for Osteoporosis.

Harry K. Genant (Chairman) , Cyrus Cooper (Rapporteur) , Gyula Poor (Rapporteur) , Ian Reid (Rapporteur) , George Ehrlich (Editor), J. Kanis (Editor), B. E. Christopher Nordin (Editor), Elizabet h Barrett-Connor , Dennis Black, J.-P. Bonjour, Bess Dawson-Hughes , Pierre D. Delmas, J. Dequeker , Sergio Ragi Eis, Carlo Gennari , Olaf Johnell , C. Conrad Johnston, Jr, Edith M. C. Lau, Uri A. Liberman, Robert Lindsay, Thomas John Martin, Basel Masri, Carlos A. Mautalen, Pierre J. Meunier, Paul D. Miller , Ambrish Mithal, Hirotoshi Morii , Socrates Papapoul os, Anthony Woolf, Wei Yu and Nikolai Khaltaev (WHO Secretariat) 30

Calcium and osteoporosis

The loss of bone which starts at the menopause is self-limiting (exponential) and possibly mainly trabecular. It merges into an age-related linear loss of bone which is probably mainly cortical. The menopause is associated with a rise in obligatory urinary calcium loss resulting from an increase in the filtered load of calcium which may be due to the complexed fraction. The dependence of the urinary hydroxyproline on the urinary calcium and sodium suggests that the bone resorption is a response to calcium losses rather than a primary event. In osteoporotic women, there is a further increase in filtered load of calcium and obligatory calcium loss, frequently coupled with malabsorption of calcium. Urinary hydroxyproline can be suppressed by calcium administration in those with normal absorption and by calcitriol in those with calcium malabsorption. It is known that calcium deficiency causes osteoporosis in experimental animals, but there is controversy about the role of calcium deficiency in the pathogenesis of human osteoporosis. Calcium supplementation inhibits cortical bone loss in postmenopausal women but there is some doubt as to whether it can inhibit trabecular bone loss in women close to the menopause. This may be partly a matter of dose, formulation and time of administration.

Vitamin D Metabolites and Calcium Absorption in Severe Vitamin D Deficiency

Contrary to frequent claims, vitamin D insufficiency does not generally cause malabsorption of calcium because serum 1,25(OH)2D, which is the major determinant of calcium absorption, is maintained by secondary hyperparathyroidism. Nevertheless, because malabsorption of calcium has been described in osteomalacia, there must be a 25(OH)D level below which the serum 1,25(OH)2D can no longer be sustained, although it has never been defined. This paper seeks to define it. We examined the records of 3661 patients and found 319 with a serum 25(OH)D ≤40 nM, in whom calcium absorption, serum calcium, PTH, bone markers, and vitamin D metabolites had been measured. They were grouped according to their serum 25(OH)D into four categories, 0–10, 11–20, 21–30, and 31–40 nM, and differences between the groups were tested by ANOVA. Correlations between the variables were also examined. Serum calcium, 1,25(OH)2D, and calcium absorption were significantly decreased and serum PTH and alkaline phosphatase (ALP) and urine hydroxyproline were increased in those with 25(OH)D ≤10 nM. Serum ALP and urine hydroxyproline were more strongly related, inversely, to calcium absorption than to the vitamin D metabolites. We conclude that vitamin D deficiency does not reduce serum 1,25(OH)2D, and therefore calcium absorption, until the serum 25(OH)D falls to ∼10 nM. At this level, the substrate concentration seems to be insufficient to maintain the level of the dihydroxy metabolite despite secondary hyperparathyroidism. Further studies are needed to see how these changes correlate with the histological changes of osteomalacia.

Misconceptions — Vitamin D insufficiency causes malabsorption of calcium

The negative effect of vitamin D insufficiency on bone is commonly attributed to a decrease in calcium absorption although little evidence has been produced to support this assumption. Using two previously published series of elderly patients we refute this common assumption and present evidence that low circulating levels of 25 hydroxyvitamin D have a direct and deleterious effect on bone.

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.

Nutrition, Osteoporosis, and Aging

ABSTRACT: Loss of bone is an almost universal accompaniment of aging that proceeds at an average rate of 0.5‐1% per annum from midlife onwards. There are at least four nutrients involved in this process: calcium, salt, protein, and vitamin D, at least in women. The pathogenesis of osteoporosis in men is more obscure. Calcium is a positive risk factor because calcium requirement rises at the menopause due to an increase in obligatory calcium loss and a small reduction in calcium absorption that persist to the end of life. A metaanalysis of 20 calcium trials shows that this process can generally be arrested by calcium supplementation, although there is some doubt about its effectiveness in the first few years after menopause. Salt is a negative risk factor because it increases obligatory calcium loss; every 100 mmol of sodium takes 1 mmol of calcium out of the body. Restricting salt intake lowers the rate of bone resorption in postmenopausal women. Protein is another negative risk factor; increasing animal protein intake from 40 to 80 g daily increases urine calcium by about 1 mmol/day. Low protein intakes in third world countries may partially protect against osteoporosis. Vitamin D (sometimes called a nutrient and sometimes a hormone) is important because age‐related vitamin D deficiency leads to malabsorption of calcium, accelerated bone loss, and increased risk of hip fracture. Vitamin D supplementation has been shown to retard bone loss and reduce hip fracture incidence in elderly women.

Effects of norethisterone on bone related biochemical variables and forearm bone mineral in post-menopausal osteoporosis

OBJECTIVE Progestogens may be a useful therapeutic alternative to oestrogen in the treatment of post‐menopausal osteoporosis. The purpose of this study was to determine the effects of norethisterone on forearm bone mineral content and bone related biochemical variables in patients with post‐menopausal osteoporosis.

The relation between forearm and vertebral mineral density and fractures in postmenopausal women

Vertebral and forearm mineral density (VMD and FMD, respectively) were determined in 124 postmenopausal women with no crushed vertebrae or peripheral fractures, 51 who had sustained peripheral fractures only since the menopause, 62 with vertebral compression(s) only and 75 with both types of fracture. There was a very significant correlation between the two measurements in the whole set. The scatter could not be accounted for by methodological error but was partly accounted for by body weight, since VMD was related to body weight and FMD was not. Whatever criterion was used for the diagnosis of osteoporosis (whether fracture or density) the percentage of misclassified cases was very similar by the two methods. However, VMD was relatively more reduced than FMD in vertebral fracture cases and FMD was marginally more reduced than VMD in peripheral fracture cases. There is little to choose between vertebral and forearm density in the diagnosis of osteoporosis but vertebral densitometry is slightly superior to forearm densitometry in describing the severity of osteoporosis in vertebral fracture patients.

Fracture rates as a function of forearm mineral density in normal postmenopausal women: Retrospective and prospective data

SummaryFracture histories were obtained from 492 normal postmenopausal women in 1983 and again in 1988, and related to forearm mineral content and density determined in 1983. All peripheral fractures, except those attributable to road traffic accidents, were included. There was only one hip fracture in the series. The total number of postmenopausal fractures was 183 in 149 subjects. In both the retrospective and prospective studies, fracture rates were inversely related to bone status and more significantly to bone density than to bone mass. In the pooled data, the fracture rate was three times as high in women with bone densities more than 4 standard deviations below the young normal mean as in those with bone densities above the mean. On logistic regression, the adjusted relative risk of fracture (odds ratio) in subjects more than 4 standard deviations below the young mean compared with those above the mean was 5.5 (2.7–11.4).

Relationship between plasma calcium fractions, other bone-related variables, and serum follicle-stimulating hormone levels in premenopausal, perimenopausal, and postmenopausal women

The study comprises 186 untreated normal premenopausal, perimenopausal, and postmenopausal women in whom we measured serum follicle-stimulating hormone and a number of bone-related plasma and urinary variables. The calcium fractions in the plasma were calculated from the total calcium, albumin, globulin, anion gap, and bicarbonate concentrations. With a level of follicle-stimulating hormone within the reference range (up to 20 U/L) to define the premenopausal state, we confirmed previously reported menopausal rises in plasma calcium, phosphate, alkaline phosphatase, and bicarbonate, and in urinary calcium and hydroxyproline. However, inspection of the data, and t testing at different follicle-stimulating hormone criteria showed that these changes in bone-related variables did not generally occur until the level of follicle-stimulating hormone exceeded approximately 50 U/L. The plasma alkaline phosphatase level rose earlier than the other variables and was significantly elevated in subjects with follicle-stimulating hormone values above 30 U/L. The rise in plasma calcium was mainly a result of a rise in the ultrafiltrable fraction, which in turn was accounted for by rises in the ionized and complexed fractions, of which the complexed fraction was the most significant and proportionately the largest. The rise in the complexed fraction was accounted for by the increase in plasma bicarbonate.