B. E. C. Nordin

Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women

Objective  Because it has been reported that vitamin D, given to mother or infant, can prevent type I diabetes in children, that diabetes is more common in adults with low serum vitamin D and that insulin secretion and action are related to vitamin D levels in healthy young adults we examined the relationship between serum vitamin D metabolites and fasting serum glucose in patients attending our outpatient clinics.

The definition and diagnosis of osteoporosis.

A we are inclined to think of osteoporosis as a modern disease, particularly in view of its apparently greater prevalence in the more prosperous societies of the world, the contribution of bone fragility to fractures in the elderly has been known for at least 200 years. It is difficult to say when the term “osteoporosis” was first used in the modern sense, but it was certainly employed by pathologists in the mid-nineteenth century and was clearly distinguished from osteomalacia by Pommer almost exactly 100 years ago. At the clinical level the crush fracture syndrome was still being confused with osteomalacia in the 1930’s, but by the end of that decade Albright had definitively identified it with osteoporosis, which he defined as “too little calcified bone,” and his teaching has been amply confirmed. We now recognize that osteoporosis is not only the principal cause of spontaneous vertebral compression but is also a major contributor to most fractures in the elderly. It is also common ground that osteoporosis represents a reduction in the volume of bony tissue relative to whole bone volume. Histomorphometry has established this concept beyond all reasonable doubt by showing that crush fractures in the spine are generally associated with trabecular bone volumes in the iliac crest below about 15% compared with volumes in normal young adults of about 20 to 30%. From this, it has become common practice to equate vertebral compression with osteoporosis and to use it in the selection of patients for clinical trials. It has proved a useful approach which was justified in the 1970’s when bone densitometry was in its infancy but has been extrapolated to the point where a fracture (any fracture) is considered essential to the diagnosis of osteoporosis –or even diagnostic of it. This practice is not only undesirable but positively misleading. While it is true that spontaneous vertebral compression, because it is spontaneous, generally denotes the presence of severe osteoporosis, this is not true of other fractures, which nearly always involve an element of trauma. Whether a bone breaks or not depends on the relation between the severity of the trauma and the strength of the bone, the main determinant of which is its “density,” i.e., its relative content of bony tissue. What osteoporosis does is to increase the fracture risk, not cause the fracture. It is a simple matter to show, by comparing fracture and nonfracture cases, that fracture risk is a continuous variable which rises as bone density falls, though not, of course, in a simple linear manner. As indicated above, the invoking of a fracture to justify a diagnosis of osteoporosis dates from the days before high precision densitometry; it should no longer be the practice of specialists with access to the new technology. There was a time when hyponatremia was recognized from The definition and diagnosis of osteoporosis

Calcium absorption in normal and osteoporotic postmenopausal women

SummaryHourly fractional absorption of radiocalcium (alpha), serum calcitriol, and a number of other variables were measured in 152 normal and 148 osteoporotic postmenopausal women. Alpha, body weight, and serum albumin were all significantly lower in the osteoporotic than in the normal women, and plasma alkaline phosphatase, fasting urinary calcium, sodium, and hydroxyproline were all significantly higher in the osteoporotic than in the normal group. The most significant determinant of alpha in each group was the serum calcitriol concentration, but calcium absorption relative to serum calcitriol was significantly lower in the osteoporotic than in the normal women. The serum calcitriol level was slightly but not significantly lower in the osteoporotic than in the normal group and accounted for only 20% of the difference in alpha between them. The implied “resistance” to calcitriol in the osteoporotic group was significantly related to serum albumin and body weight but independent of age. Urinary hydroxyproline was an inverse function of alpha and a positive function of fasting urinary calcium in the osteoporotic group.

Osteoporosis and Klinefelter’s Syndrome

objective We wanted to measure forearm mineral density and bone‐related biochemical variables in patients with Klinefelters syndrome.

Malabsorption of calcium in corticosteroid-induced osteoporosis

SummaryWe have examined the relation between radiocalcium absorption and serum 1,25-dihydroxy-vitamin D [1,25(OH)2D3] levels in a set of 60 postmenopausal women on corticosteroid therapy (29 with and 31 without vertebral compression fractures) and compared these results with those from 31 normal postmenopausal women age-matched with the “normal” corticosteroid-treated women. Radiocalcium absorption was a function of serum 1,25(OH)2D3 in both corticosteroid-treated groups and in the set as a whole, but the impaired calcium absorption in the corticosteroid-treated patients with osteoporosis was not accounted for by their slightly reduced serum 1,25(OH)2D3 levels. This apparent resistance to the intestinal action of 1,25(OH)2D3 was quantified by a Z score which expresses, in standard deviation units, the difference between the measured calcium absorption and that predicted from the 1,25(OH)2D3 level. The Z score was significantly reduced in the osteoporotic group. Vertebral mineral density (VMD) was measured by quantitative computed tomography in 43 of the corticosteroid-treated cases and in all the normal postmenopausal women; analysis by VMD yielded similar conclusions.

Relative contributions of years since menopause, age, and weight to vertebral density in postmenopausal women

Vertebral mineral density (VMD) was measured by quantitative computerized tomography (QCT) in 16 premenopausal and 243 untreated postmenopausal women without vertebral compression. The mean VMD in the premenopausal group was 157 +/- 10.1 mg/mL, which is close to previously reported values. In the postmenopausal women, VMD fell significantly with age and years since menopause (YSM) separately and together, but the relation to YSM was more significant than that to age. After logarithmic transformation of YSM, the fall in bone density with logYSM was highly significant (P less than 0.001), and that with age was not quite significant. In 36 pairs of women matched for YSM, there was no significant difference in VMD between the subjects up to and over 55 yr of age. In 32 pairs matched for age, VMD was significantly lower in those over 55 yr than in those up to 55 yr (P = 0.005). There was also a significant correlation between VMD and body weight. After this was allowed for, the correlation between VMD and logYSM remained highly significant, but the correlation with age was not significant. We conclude that the fall in vertebral body trabecular bone in postmenopausal women is self-limiting, amounts to about 35% bone loss in 25 yr (most of it in the first 5 yr), and corresponds to but is proportionately greater than the trabecular component in postmenopausal forearm bone loss.

Relationships Between Intestinal Calcium Absorption, Serum Vitamin D Metabolites and Smoking in Postmenopausal Women

Abstract: Smoking has been associated with low bone density, fractures and poor intestinal calcium absorption. Calcium absorption is a critical factor in calcium balance in postmenopausal women but the mechanisms causing decreased absorption efficiency in postmenopausal smokers are controversial and poorly defined. We performed a cross-sectional study of 405 postmenopausal women attending a clinic for the management of osteoporosis to compare intestinal calcium absorption efficiency, serum vitamin D metabolites and parathyroid hormone levels in postmenopausal women who had never smoked, who were smokers previously or who were current smokers, to examine the relationships between these variables in smokers. Two hundred and fifty-two of the women had never smoked, 79 had smoked previously and 74 were current smokers. The hourly fractional rate of calcium absorption was similar in non-smokers and those who had previously smoked. Radiocalcium absorption was less in the 74 smokers compared with the 331 non-smokers [0.60 (0.29 SD) vs 0.71 (0.27); p= 0.004], as were serum calcitriol (p<0.001) and parathyroid hormone (PTH) (p<0.01). There was no difference in the relationship between calcium absorption and serum calcitriol between smokers (r= 0.38) and non-smokers (r= 0.28); hence the impaired calcium absorption in the smokers was almost entirely attributable to suppression of the PTH–calcitriol endocrine axis. In postmenopausal women smoking is associated with a reduction in calcium absorption efficiency due to suppression of the PTH–calcitriol axis. This impairment of calcium absorption could lead to accelerated bone loss and limit the usefulness of dietary calcium supplementation.

Renal Effects of Calcitonin

Porcine calcitonin in a slow-release gelatin vehicle was given by intramuscular injection to 10 patients—four with primary hyperparathyroidism, four with Pagets disease, and two with carcinoma of the breast and hypercalcaemia. All cases showed a fall in serum calcium with an immediate rise in urine calcium. All except three patients with primary hyperparathyroidism showed a fall in serum phosphorus, but an immediate rise in urine phosphorus occurred in all cases. Urine hydroxyproline output fell in three patients with severe Pagets disease. Urine sodium rose in all cases, but the effects on potassium, magnesium, water, and pH were not appreciably different from results obtained in four control subjects who were given the gelatin vehicle alone. The data suggest that calcitonin caused a decrease in the tubular resorption of calcium and phosphorus. The hypocalcaemic effect appeared to be due to a decrease in bone resorption in the patients with Pagets disease but in the remaining cases could be accounted for in part or entirely by the rise in urine calcium.

Biochemical Variables in Pre- and Postmenopausal Women: Reconciling the Calcium and Estrogen Hypotheses

Abstract: There is controversy as to whether the rise in urinary calcium at the menopause is the cause or the result of the rise in bone resorption at that time. In an attempt to resolve this issue, we have compared the relevant biochemical variables in 102 premenopausal volunteers (mean age 37 years; range 21–52) and 86 apparently normal postmenopausal women (mean age 55 years; range 40–60). We measured the fasting serum calcium, creatinine, proteins, electrolytes and intact parathyroid hormone (PTH), and the urinary calcium and creatinine both after an overnight fast and in a 24-h collection. We calculated serum calcium fractions, creatinine clearance and the notional tubular maximum reabsorptive capacity for calcium. Creatinine excretion and clearance were lower in the post- than in the premenopausal women after correction for surface area and age. Total serum calcium was higher in the post- than in the premenopausal women but this was accounted for by the higher ligand concentrations in the former. Fasting and 24-h urinary calcium were also higher in the post- than in the premenopausal women due in part to the former’s higher filtered load of calcium (due to their higher serum complexed calcium) but mainly to their reduced tubular reabsorption of calcium despite their slightly raised serum PTH. Our analysis resolves the rise in urinary calcium at the menopause into its two components: increased filtered load and reduced tubular reabsorption. The changes in these two variables, neither of which can be attributed to increased bone resorption, produce an increase in calcium requirement that is sufficient to account for postmenopausal bone loss. However, the translation of this menopausal increase in calcium requirement into an increase in bone resorption at near-normal serum PTH levels requires some menopause-dependent change in the responsiveness of the bone to calcium demand. We suggest that this change may occur at the level of the osteoclasts and that estrogen may modify the calcium feedback setpoint in these cells in a manner analogous to calcitonin. This model resolves the apparent conflict between the estrogen and calcium hypotheses and explains the synergism between these two treatment modalities.

Effects of nandrolone decanoate on forearm mineral density and calcium metabolism in osteoporotic postmenopausal women

SummaryAlthough anabolic steroids have been used for many years to treat osteoporosis there is little available evidence about their efficacy or mode of action. These agents have recently been shown to produce an increase in total body calcium and bone density and it has been suggested that they stimulate bone formation. In this study 27 osteoporotic postmenopausal women were given 50 mg of nandrolone decanoate intramuscularly, every 2 or 3 weeks for 3 months, and the changes in forearm mineral density, fasting plasma, and urinary calcium, urinary hydroxyproline, and radiocalcium absorption were measured. Associated with a rise in forearm mineral density was a significant fall in fasting urinary calcium, but no significant change in fasting urinary hydroxyproline. The plasma calcium and phosphate fell significantly and there was a significant rise in the renal tubular reabsorption of calcium and a fall in the renal tubular reabsorption of phosphate. In a subset of 22 patients there was a significant rise in radiocalcium absorption. The results are consistent with the concept that nandrolone exerts a significant positive effect on bone formation and that this results in a fall in the fasting plasma calcium level, and consequently calcium excretion.