Christopher Nordin

Royal Adelaide Hospital | RAH · Department of Endocrinology

Research into metabolic bone disease has made remarkable progress over the last 20 years, with the identification of numerous new molecules and pathways regulating bone cells as well as their plasma milieu. Their activities are largely regulated by the physiological status of the body incorporating the biochemical, physical and mechanical functions...

One of the remarkable features of the paper by Bolland and colleagues on the risk from calcium supplementation and vitamin D is its failure to draw attention to the hazard ratio of 0.84 in favour of calcium supplements for deaths from all causes in the “any personal …

Detailed consideration of the suggested association between calcium supplementation and heart attacks has revealed weakness in the evidence which make the hypothesis highly implausible. The aim of this study was to evaluate the strength of the evidence that calcium supplementation increases the risk of myocardial infarction. This study used critica...

Reports of adverse events related to calcium supplementation should be supported by rigorous evidence.

There is uncertainty about the calcium requirement with particular respect to age and sex differences and the calculation of skin calcium losses. We calculated the calcium requirement of adult men from a homogenous set of calcium balances and a robust estimate of calcium loss through the skin. We reviewed available high-quality published calcium ba...

The paper by Bolland and colleagues is seriously flawed in many respects, the first being its misleading title.1 It is not a meta-analysis in the usually accepted sense—that is, a review of published trials. Most of the data are unpublished, were obtained by direct request from the relevant authors, and are impossible to investigate independently.T...

Osteoporosis is the index disease for calcium deficiency, just as rickets/osteomalacia is the index disease for vitamin D deficiency, but there is considerable overlap between them. The common explanation for this overlap is that hypovitaminosis D causes malabsorption of calcium which then causes secondary hyperparathyroidism and is effectively the...

We compared the effects of oral calcium and vitamin D separately and together on relevant variables in 22 postmenopausal volunteers with initial serum 25OHD levels below 60 nmol/L. Subjects were allocated randomly to two regimens: group 1 received 1 week of calcium 1,000 mg, followed by 7 weeks with additional vitamin D3 1,000 i.u. daily; group 2 r...

We challenge the widespread assumption that malabsorption of calcium per se causes secondary hyperparathyroidism. Serum parathyroid hormone (PTH) does not rise at the menopause despite the fall in calcium absorption, nor is it raised in osteoporotic women with vertebral fractures despite their low calcium absorption. The age-related rise in serum P...

This study was conducted to compare the suppressive effects of calcium carbonate and calcium citrate on bone resorption in early postmenopause. Calcium citrate is thought to be better absorbed. We therefore tested the hypothesis that calcium as citrate is more effective than calcium as carbonate in suppressing parathyroid hormone (PTH) and C-termin...

Determining risk is the first step in deciding on appropriate management.

Contrary to frequent claims, vitamin D insufficiency does not generally cause malabsorption of calcium because serum 1,25(OH)(2)D, 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 belo...

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 ha...

Assumptions And DefinitionsObservationsConclusions ReferencesDiscussionReferences

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Impaired gut sensitivity to 1,25-dihydroxyvitamin D (1,25(OH)(2)D), 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...

The relation between fracture risk and bone mineral density (BMD) is commonly expressed as a multiplicative factor which is said to represent the increase in risk for each standard deviation fall in BMD. This practice assumes that risk increases multiplicatively with each unit fall in bone density, which is not correct. Although odds increase multi...

The relation between fracture risk and bone density is frequently defined in terms of a relative hazard derived from the Cox proportional hazards model. The relative hazard is a multiplicative factor representing the rise in hazard for each standard deviation fall in bone mineral density, which has a typical value of about 1.5. It is not generally...

To determine the effects of menopause on bone-related variables in Indonesian women and to compare them with corresponding data in Caucasian Australian women. A study of bone-related variables in women aged 45-55 years in Jakarta compared with corresponding historical data from Caucasian Australian women. Dietary intakes, bone mineral density (BMD)...

Low vitamin D levels are common. Bone biopsies taken from 121 ambulant patients were therefore reviewed. Seasonal changes in mineralization correlated inversely with serum 25-hydroxyvitamin D but not the more active metabolite, 1,25-dihydroxyvitamin D. This implies that the latter is produced in bone. It has been 30 yr since a seasonal variation in...

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...

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 se...

It is assumed that calcium absorption decreases with age, but this is not well documented. We report a study that addresses this issue. The aim was to establish the extent and timing of any age-related change in calcium absorption in postmenopausal women. We measured radiocalcium absorption (alpha) in 262 healthy postmenopausal women aged 40-87 y....

To evaluate the effects of the menopause on bone-related biochemical variables in a longitudinal study. Recruitment by advertisement of premenopausal women over the age of 44 for measurement of selected variables and collection of blood and urine samples for deep freezing, followed by annual check of menopausal status and repeat collection of blood...

It has been known for many years that serum PTH rises with age, and it has been suggested that this rise may contribute to bone loss in postmenopausal women. It has been variously attributed to declining renal function, declining calcium absorption efficiency, and declining serum 25-hydroxyvitamin D [25(OH)D] levels. We studied the effects of age,...

Intestinal calcium absorption accounts for 60% of the variance in calcium balance and is therefore a potentially very important determinant of bone status. Whether measured by the balance technique or with radiocalcium, it is known to be significantly reduced in postmenopausal women with vertebral and hip fractures. By contrast, there is very littl...

It is known that nursing-home patients with vitamin D insufficiency have elevated serum parathyroid hormone (PTH) as well as raised serum alkaline phosphatase (ALP). Although it is well known that vitamin D insufficiency and secondary hyperparathyroidism are common among the elderly in western countries, there is continuing controversy over the lev...

The objective of this study was to determine the pattern of forearm bone loss and its relationship to markers of bone turnover and sex steroids in normal men. This was a longitudinal study over a median interval of 41 months. The study was conducted in Adelaide, Australia. Study participants were 123 healthy male subjects, between the ages of 20 an...

Bone resorption follows a circadian rhythm that peaks at night, reflecting the circadian rhythm of serum parathyroid hormone. Our previous studies in early postmenopausal women have established that 1000 mg of calcium given at 9 p. m. reduced bone resorption markers overnight, but not during the day. In contrast, 1000 mg given as a divided dose (50...

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...

Calcium is critically important in a diverse number of physiological processes, necessitating close regulation of its intracellular and extracellular concentration. This demands the interplay of two principal hormones, parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D3 (calcitriol) and three body organs, the gut, the kidney and bone, which act...

Low serum 25-hydroxyvitamin D ¿25(OH)D concentrations are commonly found in the elderly and are associated with hip fracture. Treatment with vitamin D and calcium can reduce the risk of fracture. The relation between the rise in parathyroid hormone (PTH) with age and the decrease in 25(OH)D is not clear. Neither is there any consensus on the serum...

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Osteoporosis can be defined in terms of apparent bone density and can be determined by densitometry. But differences between reference standards and instruments make standardization difficult. Conventional classification schemes are not applicable but analysis by risk factors does permit a systematic approach.

We tested the hypothesis that the age-related decline in skin thickness may contribute to the age-related decline in serum 25-hydroxyvitamin D [25(OH)D]. We measured skinfold thickness on the back of the hand, serum 25(OH)D, height, and weight in 433 normal postmenopausal women. We also noted the average daily hours of sunlight in the month in whic...

We tested the hypothesis that the age-related decline in skin thickness may contribute to the age-related decline in serum 25-hydroxyvitamin D [25(OH)D]. We measured skinfold thickness on the back of the hand, serum 25(OH)D, height, and weight in 433 normal postmenopausal women. We also noted the average daily hours of sunlight in the month in whic...

Orally or parenterally administered sodium is known to increase urinary calcium in experimental animals and humans, and there is well-documented correlation between urinary sodium and calcium in 24-h urine collections from normal subjects and renal stone formers. The correlation between urinary sodium and calcium is generally sodium driven, i.e., i...

The metabolic effects of oophorectomy (Oophx) were studied in 6-month-old rats maintained on a normal chow diet. Nine weeks following operation, Oophx animals had a significantly lower femoral trabecular bone volume (BV/TV) than sham-operated animals; mean (SD) Oophx 8.5 (3.8)%; Sham 13.4 (2.5)%; P = 0.013). They also had a higher urine hydroxyprol...

Bone “density” (bone mass/bone volume) declines with age from the menopause in women and from about age 55 in men. This fall in bone density (osteoporosis) weakens the bones and leads to a progressive rise in fracture rates, particularly in women. Many risk factors contribute to the bone-losing process, but one which attracts increasing attention i...

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 ag...

We wanted to measure forearm mineral density and bone-related biochemical variables in patients with Klinefelter's syndrome. Measurements made in patients with Klinefelter's syndrome were compared to those obtained in age-matched normal male volunteers. We studied 22 patients with Klinefelter's syndrome (12 of whom had received sex hormone therapy)...

Hourly 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, sodi...

Fracture 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 fractu...

Female Sprague-Dawley rats (n=72), 6 months old, underwent either sham operation, oophorectomy, adrenalectomy, or combined oophorectomy and adrenalectomy (O&A). They were all maintained on normal salinead libitum and 20 g/day 1.1% calcium chow. Nine weeks after operation, the trabecular bone volume of the distal femoral shaft was significantly lowe...

The effects of oral calcitriol (0.25 and 0.50 micrograms/d), together with calcium (1 g/d), on calcium absorption and bone resorption were measured in postmenopausal osteoporotic women with calcium malabsorption. Radiocalcium absorption was significantly improved and urinary hydroxyproline/creatinine excretion significantly reduced on both doses, b...

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 betwee...

• The effects of norethindrone (5 mg daily) on biochemical variables and forearm mineral density were assessed in 20 postmenopausal women with mild primary hyperparathyroidism. Norethindrone produced a significant fall in plasma calcium levels and the fasting urinary calcium-creatinine and hydroxyproline-creatinine ratios after three months of trea...

• The prevalence of lactase deficiency and the relationship between lactose and calcium malabsorption in postmenopausal osteoporosis has been assessed in 46 subjects. Malabsorption of lactose occurred in 25 (54%) of the subjects and was associated with a significantly lower milk intake. Malabsorption of calcium occurred in 11 (44%) of the lactase-d...

When Klinefelter et al. originally described their syndrome in 1942, they made no reference to osteoporosis. Since that time it has frequently been claimed that osteoporosis is a factor of the syndrome, but there is a shortage of hard data on the subject. It is probably true that osteoporosis is associated with hypogonadism in men (Jackson 1958), b...

Calcium malabsorption is common in the elderly and may contribute to the development of age-related bone loss. To investigate its cause, we have measured radio-calcium absorption, plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone in forty-eight elderly women with a normal plasma creatinine. Calcium malabsorption was associ...

A cross-sectional study of plasma 25-hydroxy-vitamin D (25OHD) concentrations in healthy women in the age range 20–96 years is reported. Mean values decline with increasing age while abnormally low levels of plasma 25OHD are more common in the elderly. The decline in vitamin D status with age is probably the result of lack of sunlight exposure asso...

Calcium is the principal constituent of most kidney stones, which seems to originate as a crystalline precipitate in a supersaturated medium. Calcium concentration in the urine therefore plays an important part in the genesis of calcium stone disease and is of course determined by the relation between the rate of calcium excretion and the rate of u...

A sensitive method has been developed for measuring the effect of inhibitors of crystallisation on the growth and aggregation of calcium oxalate crystals in vitro. Of the known inhibitors tested the highly charged anions pyrophosphate and ethane-1-hydroxy-1,1-diphosphonate (EHDP) were effective down to concentrations of 0.1–1 μmole/l and the polyan...

The investigation and classification of any patient with respect to urinary calcium excretion requires the measurement of the 24 hr calcium output on low and normal calcium intakes (150 and 100 mg Ca) and of the fasting plasma and urinary calcium and creatinine. Such investigation shows that hypercalciuria may be absolute or relative. Absolute hype...

PEARSON1 has recently presented evidence which suggests, that human urine may contain appreciable quantities of non-exchangeable calcium. Urine, labelled with calcium-47 in calcium chloride, was passed through a column of `Zeokarb 225' cation exchange resin and the effective non-exchangeable calcium (CNE) was calculated, using the following express...