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Knowledge of the pre-rehabilitation generic status of functioning in individuals with low back pain is necessary to understand the clinical utility of rehabilitation care. We conducted a scoping review to describe the pre-rehabilitation functioning status of persons with nonspecific low back pain using the World Health Organization Disability Assessment Schedule (WHODAS)-36 or WHODAS-12. We searched multiple databases from 2010 to 2021 for studies reporting pre-rehabilitation scores using WHODAS in persons with low back pain. Reviewers independently screened articles and extracted data, and we descriptively summarized results by the duration of low back pain (acute/subacute3 months; chronic ≥3 months), and the WHODAS version. Of 1770 citations screened, eight citations were relevant. Five studies were conducted in Europe, two in America, and one in the African Region (mostly high-income countries). In persons with acute low back pain, the mean WHODAS-36 pre-rehabilitation summary score (complex scoring) was 22.8/100 (SD = 15.4) (one study). In persons with chronic low back pain, the mean WHODAS-36 summary score (complex scoring) ranged from 22.8/100 (SD = 5.7) to 41.5/100 (SD = 13.8) (two studies). For WHODAS-12 in persons with chronic low back pain, the mean summary score was 11.4/48 (SD = 8.7) or 14.4/48 (SD = 9.4) using simple scoring (two studies), and 25.8/100 (SD = 2.2) using complex scoring (one study). No floor or ceiling effects were observed in WHODAS-36 summary scores for chronic low back pain. Our scoping review comprehensively summarizes available studies reporting pre-rehabilitation levels of functioning using WHODAS in persons with low back pain. Persons with low back pain seeking rehabilitation have moderate limitations in functioning, and limitations level tends to be worse with chronic low back pain.

To determine the measurement properties and minimal important change (MIC) of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) short (12 questions) and full (36 questions) versions in persons with nonspecific low back pain (LBP).MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, APA PsycInfo, and Cochrane Central Register of Controlled Trials (inception to May 2021).Eligible studies assessed measurement properties or MIC of WHODAS 2.0 in persons with LBP.Paired reviewers screened articles, extracted data, and assessed risk of bias using Consensus-Based Standards for Selection of Health Measurement Instruments (COSMIN) and COSMIN-Outcome Measures in Rheumatology checklists.We descriptively synthesized results stratified by measurement property and LBP duration (subacute: 6 weeks to 3 months; chronic: ≥3 months).We screened 297 citations and included 14 studies (reported in 15 articles). Methodological quality of studies was very good for internal consistency and varied between very good and doubtful for construct validity, doubtful for responsiveness, and adequate for all other properties assessed. Evidence suggests that WHODAS 2.0 full version has adequate content validity (2 studies); WHODAS 2.0 short and full versions have adequate structural validity (3 studies), but construct validity is indeterminate (9 studies). WHODAS 2.0 short and full versions have adequate internal consistency (10 studies), and the full version has adequate test-retest and interrater reliability (3 studies) in persons with LBP. Minimal detectable change (MDC) was 10.45-13.99 of 100 for the full version and 8.6 of 48 for the short version in persons with LBP (4 studies). WHODAS 2.0 full version has no floor or ceiling effects, but the short version has potential floor effects in persons with chronic LBP (3 studies). One study estimated MIC for the full version as 4.87 of 100 or 9.74 of 100 (corresponding to 1- and 2-point change on 0- to 10-cm visual analog scale for pain, respectively), and 1 study estimated 3.09-4.68 of 48 for the short version.In persons with LBP, WHODAS 2.0 full version has adequate content validity, structural validity, internal consistency, and reliability. WHODAS 2.0 short version has adequate structural validity and internal consistency. Construct validity of the short and full versions is indeterminate. Since MDC is estimated to be larger than MIC, users may consider both MIC and MDC thresholds to measure change in functioning for LBP.

In recent years attention has turned from the rather limited problem of vertebral crush fractures in postmenopausal women to a wider study of the effects of age on bone in general and is now turning to the specific role of the menopause in the light of the wider experience which has been gained. The ossifying effect of estrogens on the bone marrow of mice was shown to be similar to that in pigeons, and was also shown to be inhibited by testosterone. The loss of bone appears to be due to an increase in bone resorption rather than to a decline in bone formation, and its biochemical manifestations are reversible with estrogens. Until recently no biochemical differences involving calcium and phosphorus metabolism had been detected between pre- and postmenopausal women. The underlying mechanisms are only poorly understood, but present data are compatible with the concept that estrogens reduce the sensitivity of bone to the resorbing action of parathyroid hormone.

Women tend to have smaller lungs than men of the same size as well as narrower airways compared to men when matched for the same lung size. Additionally, women with smaller airways relative to lung size are more likely to experience expiratory flow limitation (EFL) as well as exercise-induced arterial hypoxemia (EIAH). One of the possible causes of EIAH includes excessive widening in the alveolar-to-arterial oxygen pressure difference (A-aDO2) due to diffusion limitation. This study investigated if lung diffusing capacity (D LCO) is lower in women with EFL compared to non-flow limited (NEFL) women during exercise. D LCO was measured using the rebreathing technique at rest and at 40, 60, and 80 % of $$\dot{V}{\text{O}}_{2\text{max}}$$ on a treadmill in healthy women with EFL (n = 7; 21.6 ± 2.3) and without EFL (NEFL, n = 9; 21.2 ± 2.3). Arterial oxygen saturation was measured using pulse oximetry (SpO2). There was no difference (p > 0.05) in D LCO between groups at rest or during exercise; however, SpO2 was significantly lower in the EFL females compared to NEFL females during exercise. Due to the lack of differences in D LCO between women with EFL and without EFL, our results suggest that this is not a possible cause for the significant differences in SpO2 between the two groups.

Recent clinical studies show that hypoglycaemia is associated with increased risk of death, especially in patients with coronary artery disease or acute myocardial infarction. This paper reviews data from cellular and clinical research supporting the hypothesis that acute hypoglycaemia increases the risk of malignant ventricular arrhythmias and death in patients with diabetes by generating the two classic abnormalities responsible for the proarrhythmic effect of medications, i.e. QT prolongation and Ca(2+) overload. Acute hypoglycaemia causes QT prolongation and the risk of ventricular tachycardia by directly suppressing K(+) currents activated during repolarisation, a proarrhythmic effect of many medications. Since diabetes itself, myocardial infarction, hypertrophy, autonomic neuropathy and congestive heart failure also cause QT prolongation, the arrhythmogenic effect of hypoglycaemia is likely to be greatest in patients with pre-existent cardiac disease and diabetes. Furthermore, the catecholamine surge during hypoglycaemia raises intracellular Ca(2+), thereby increasing the risk of ventricular tachycardia and fibrillation by the same mechanism as that activated by sympathomimetic inotropic agents and digoxin. Diabetes itself may sensitise myocardium to the arrhythmogenic effect of Ca(2+) overload. In humans, noradrenaline (norepinephrine) also lengthens action potential duration and causes further QT prolongation. Finally, both hypoglycaemia and the catecholamine response acutely lower serum K(+), which leads to QT prolongation and Ca(2+) loading. Thus, hypoglycaemia and the subsequent catecholamine surge provoke multiple, interactive, synergistic responses that are known to be proarrhythmic when associated with medications and other electrolyte abnormalities. Patients with diabetes and pre-existing cardiac disease may therefore have increased risk of ventricular tachycardia and fibrillation during hypoglycaemic episodes.

The tempo and change in bone growth during puberty in relation to physical growth is described in a cohort of 56 boys and 52 girls. Distal forearm bone width, mineral content and volumetric density, anthropometry and pubertal status were measured at ages 11, 13, 15 and 17 y, and bone age at 17 y. Bone width and mineral content increased independently with age for each pubertal stage. Volumetric density fell during early puberty and then increased rapidly. Maximal increase of all bone variables occurred earlier in girls than in boys and earliest for bone width, then mineral content, then density. In girls most change occurred in the 12 mo before and after menarche. The degree of tracking was similar to that for height. Bone growth followed physical growth but at a slower tempo. By age 17 y boys had attained 86% of the reference adult bone mineral content and volumetric density; girls had attained 93% of the reference adult bone mineral content and 94% of volumetric density. Those skeletally mature at 17 y had greater mineral content and volumetric density. To maximize peak bone mass, modifiable environmental factors should be optimized before the onset of puberty and be maintained throughout this period of rapid growth and beyond attainment of sexual maturity.

Background: Dietary factors acutely influence the rate of bone resorption, as demonstrated by changes in serum bone resorption markers. Dietary calcium exerts its effect by reducing parathyroid hormone levels while other components induce gut incretin hormones both of which reduce bone resorption markers. The impact of dietary calcium on bone turnover when energy metabolism is modulated such as in metabolic syndrome has not been explored. This study was designed investigate whether metabolic syndrome or a greater amount of visceral fat influences the impact of dietary calcium on bone turnover. Methods: The influence of the metabolic syndrome on effects of dietary calcium on bone turnover in community dwelling postmenopausal women was studied. Twenty five volunteers consumed 200 mL of low fat milk with additional 560 mg calcium (one serve of Milo®) in the evening on one occasion. Fasting morning serum biochemistry before and after the milk drink with lumber spine bone density, bone mineral content, fat and lean mass using dual energy X-ray absorptiometry (DXA) and waist circumference were measured. The women were divided into 2 groups using the waist measurement of 88 cm, as a criterion of metabolic syndrome. Student's t tests were used to determine significant differences between the 2 groups. Results: The lumbar spine mineral content was higher in women with metabolic syndrome. After consuming the milk drink, serum bone resorption marker C terminal telopeptide (CTX) was suppressed to a significant extent in women with metabolic syndrome compared to those without. Conclusions: The results suggests that dietary calcium may exert a greater suppression of bone resorption in post-menopausal women with metabolic syndrome than healthy women. Despite substantial evidence for close links between energy metabolism and bone metabolism this is the first report suggesting visceral fat or metabolic syndrome may influence the effects of dietary calcium on bone metabolism. Refereed/Peer-reviewed

With the large number of proposed liquefied natural gas (LNG) facilities in the United States (and worldwide), many new technical personnel are becoming involved in applying and interpreting LNG standards and regulations. Also, opponents of the new LNG developments are questioning whether existing safety and security requirements are adequate. In this paper, we will begin with an overview of existing standards and regulations pertinent to LNG facilities (for both onshore and offshore applications). That discussion will include documents from the National Fire Protection Association, the European Committee for Standardization, the Department of Transportation, and the United States Coast Guard. For offshore facilities, it will discuss the guidelines from some of the international classification societies. This paper will outline what is addressed (and what is not addressed) by these standards and will then focus on and discuss the issues with those requirements and the changes that are currently under consideration by the standards organizations and federal regulators. This paper finishes with some specific recommendations for consideration by LNG facility developers. © 2005 American Institute of Chemical Engineers Process Saf Prog, 2005

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 level of serum 25-hydroxyvitamin D [25(OH)D] necessary for bone health. We approached this issue by examining the relationships between serum 25(OH)D, ionized calcium, PTH, and ALP and the urinary bone resorption markers hydroxyproline, pyridinoline, and deoxypyridinoline, corrected for creatinine (OHPr/Cr, Pyd/Cr, and Dpd/Cr, respectively), in 486 postmenopausal women of mean age 63 (SD 9.5) years, who were referred to our osteoporosis and menopause clinics for investigation. When the patients were divided into two groups with 25(OH)D above and below 20 nmol/L, 30 nmol/L, 40 nmol/L, 50 nmol/L, 60 nmol/L, or 70 nmol/L, the most significant differences between the two groups thus derived was found at a serum 25(OH)D level of 60 nmol/L (P < 0.001 for all markers). The most significant difference between groups for serum PTH was found when the patients were divided at a serum 25(OH)D of 50 nmol/L. PTH, OHPr/Cr, Pyd/Cr, and ALP were inversely related to serum 25(OH)D. PTH was inversely related to serum ionized calcium. There was a trend for ionized calcium to be positively related to 25(OH)D, but this did not reach statistical significance. We conclude that rises in three bone resorption markers and ALP can be detected in postmenopausal women when the serum 25(OH)D level falls below 60 nmol/L. Levels above this may be required for optimal bone health.

To evaluate the effect of calcium intake on absorption of dietary phosphorus, with special reference to typical calcium intakes and to those likely to be encountered in prevention and treatment of osteoporosis.Two academic health sciences centers; inpatient metabolic research unit.Evaluation of calcium and phosphorus balance data obtained in two data sets, the first, 543 studies of healthy women aged 35-65, and the second, 93 men and women aged 19-78; development of multiple regression models predicting fecal phosphorus (the complement of net absorbed phosphorus); data from the two centers analyzed separately as a check on the consistency of the findings.Mean net absorption of phosphorus was 60.3% (+/- 18.1) for data set 1 and 53.0% (+/-9.4) for data set 2. Just two variables, fecal calcium and diet phosphorus, were positively and independently associated with fecal phosphorus. These variables explained 73% of the variance in fecal phosphorus in data set 1 and 33% in data set 2. Fecal calcium alone explained the lion's share of the relationship. The coefficients of the fecal calcium term in the models fitted to the data were 0.332+/-0.022 and 0.155+/-0.039, for data sets I and 2, respectively. Adjusting for the relationship between fecal calcium and calcium intake and using the parameters of the larger data set, it follows that each increase in calcium intake of 0.5 g (12.5 mmol) decreases phosphorus absorption by 0.166 g (5.4 mmol).As calcium intake increases without a corresponding increase in phosphorus intake, phosphorus absorption falls and the risk of phosphorus insufficiency rises. Intakes with high Ca:P ratios can occur with use of supplements or food fortificants consisting of non-phosphate calcium salts. Older patients with osteoporosis treated with current generation bone active agents should receive at least some of their calcium co-therapy in the form of a calcium phosphate preparation.

Background. 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 and 83 years. Methods. Fat-corrected forearm bone mineral content (fcBMC), markers of bone formation (alkaline phosphatase, osteocalcin, procollagen type 1 C-terminal extension peptide) and bone resorption (collagen type I cross-linked telopeptide, hydroxyproline/creatinine, pyridinoline/creatinine, and deoxypyridinoline/creatinine), calculated serum bioavailable testosterone, and serum estradiol were measured. Results. The mean time-weighted rate of change in forearm fcBMC was � 0.33% � 0.72 ( SD ) per year. Bone loss commenced after 30 years of age and increased with age ( p � .001), particularly after age 70 years. There was no relationship between the rate of change in fcBMC and either markers of bone turnover or serum sex steroids. Conclusions. In normal men, bone loss increases with age; there does not appear to be any relationship between this loss and either markers of bone turnover or levels of free androgen or estrogen.

We report sequential changes in bone mineral density (BMD) at the forearm, hip and spine in 340 consecutive postmenopausal women referred by 103 general practitioners and six specialists, and who were either untreated or being treated with calcium, estrogen, norethisterone or calcitriol for a median period of 25 months (range 11–52). The mean annual rate of change in BMD at the three sites was: 1.39% in 44 women on norethisterone; 0.94% in 107 women on estrogen (both p < 0.001); 0.24% (not significant) in 52 women on calcitriol; –0.53% in 92 women on calcium; and –1.06% in 45 women on no treatment (both p < 0.01). The mean annual rate of change at the three sites in the 295 treated women was 0.43%, which was significantly positive (p < 0.001) and was 1.49 percentage points more positive than in the untreated women (p < 0.001). The greatest mean difference between treated and untreated patients was seen at the forearm, where it was 2.16 percentage points (p < 0.001). This was significantly greater than the...

The successful use of the vitamin D metabolites 1-alphahydroxy and 1,25 dihydroxyvitamin D in the correction of calcium malabsorption in postmenopausal osteoporosis and the equally successful use of vitamin D itself in the prevention of bone loss and fractures in older women have tended to confuse these two treatment modalities in some sections of the scientific community. This paper will clarify this confusion by showing that the indications for treatment with vitamin D (or its 25-hydroxy metabolite) are quite distinct from the indications for treatment with what are sometimes called the “hormonal” forms of vitamin D, notably, 1-alpha and 1,25D. There is no dose of vitamin D that can replace these metabolites.

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.

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.

In order to establish whether calcium supplementation suppresses bone resorption in early postmenopausal women and whether any response is related to calcium absorption status, we studied 22 healthy women (median age 52 years) all within 5 years of the menopause. Urine was collected between 9.00 p.m. and 9.00 a.m., and 9.00 a.m. and 9.00 p.m., (2 days) and a fasting blood and spot urine sample was obtained at 9 a.m. On the first day, 5 microCi of 45Ca in 250 ml water with 20 mg calcium carrier as the chloride was given at 9.00 a.m. and a further blood sample was obtained at 10.00 a.m. to measure calcium absorption. A 1 g calcium load was given at 9.00 p.m., immediately before the second 24-hour urine collection. There was a rise in plasma ionized calcium (1.18 +/- 0.010 mmol/liter versus 1. 21 +/- 0.011 mmol/liter, P0.01) and a fall in plasma PTH (4.2 +/- 0.34 pmol/liter versus 3.5 +/- 0.31 pmol/liter, P0.01) from baseline after the calcium load, and a trend for the magnitude of the change in PTH to be inversely related to calcium absorption (r = -0.33, P = 0.13). In the fasting spot urine samples, there were falls in hydroxyproline (OHPr/Cr; 14.6 +/- 0.71 versus 12.6 +/- 0.83, P0.001), pyridinoline (Pyr/Cr; 75 +/- 2.8 versus 70 +/- 3.5, P0.05), and deoxypyridinoline (Dpd/Cr; 22.7 +/- 1.2 versus 19.5 +/- 1. 1, P0.005) after the calcium load. The calcium load suppressed urinary Dpd/Cr between 9.00 p.m. and 9.00 a.m. (P0.005), but not between 9.00 a.m. and 9.00 p.m. We conclude that acute administration of a 1 g calcium load suppresses bone resorption in early postmenopausal women, probably by decreasing PTH secretion.

The model presented in this paper is expressed diagrammatically in Fig. 1. Only those forms of osteoporosis which are secondary to increased bone resorption and only some of them can be attributed to calcium deficiency but they represent a substantial proportion of the total. It is very unlikely that there is no calcium deficiency syndrome (as Kanis [59] implies) and well documented that such a syndrome must express itself as osteoporosis. It is a remarkable fact that every osteoporosis consensus conference stresses the importance of an adequate calcium intake in the prevention and management of osteoporosis[60, 61] but none of them has remarked that calcium deficiency causes osteoporosis or spelt out the obvious consequences of inadequate calcium intake. Could it be that calcium is too cheap to command respect?

With the aim of exploring putative correlations between serum and CSF levels of clozapine and its demethyl metabolite, lumbar puncture was performed on four male and five female schizophrenic patients during long-term treatment with clozapine. Three consecutive 6-ml fractions were collected after at least 8 h of bedrest and fasting. On comparing serum and CSF levels, a correlation was found for norclozapine in the third (13-18 ml) CSF fraction. Norclozapine in the first (0-6 ml) CSF correlated significantly with height. The CSF/serum ratio of clozapine in the first fraction was correlated significantly with body weight. No correlations were found between serum levels of clozapine and norclozapine, or between the serum and CSF levels of clozapine. The study suffers from a small number of patients (for ethical reasons), but the present results might be explicable if the first (0-6 ml) CSF fraction represents a cul-du-sac of the CSF, mirroring the previous day's drug levels. The second fraction, then, will represent the CSF level in the steady state during the night.

The relationship between calcium absorption and gastric emptying and the precision of measurement of fractional calcium absorption using a single isotope technique were evaluated in 14 normal postmenopausal women (age range 61-72 years). On two occasions separated by between 5 and 15 days, each subject was given 250 mL water containing 0.2 MBq of 45Ca in 20 mg of calcium carrier as the chloride, 20 mg kg-1 paracetamol and 9 MBq of 99mTc sulphur colloid. Venous blood samples were taken at -2, 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption of the drink, and gastric emptying (GE) was monitored with a gamma camera. Fractional calcium absorption in the first hour (alpha 6) was calculated from the blood samples obtained at 15, 30, 45, 60, 90 and 120 min. An absorption rate was also derived from the 60 min sample using only a calibration curve (alpha 1). There were close correlations between radiocalcium absorption on the two study days (r = 0.89, P < 0.001 for both alpha 1 and alpha 6) and between alpha 1 and alpha 6 (r = 0.93, P < 0.001). Plasma paracetamol concentrations at 15 min were directly related to the early phase of GE (r = 0.42, P < 0.05). In contrast, calcium absorption was inversely related to GE (r = 0.45, P < 0.05). We conclude that radiocalcium absorption is not greatly influenced by gastric emptying rate and that the single blood sample procedure has similar precision to the six-blood sample test.

A total of 19 measured and derived bone-related biochemical variables were determined in 307 postmenopausal volunteers on two occasions, 5 years apart. The plasma variables with the highest coefficients of determination (r2) were plasma globulins, alkaline phosphatase, creatinine and calculated ionized and ultrafiltrable calcium. In the urine, the highest r2 values were in respect of fasting urine calcium excretion corrected for urine sodium, hydroxyproline excretion, and the maximal renal tubular reabsorption of calcium and phosphate (TmCa/GFR and TmP/GFR). The components of variance of TmCa/GFR and TmP/GFR show marked individuality but their methods determination meet the criterion for acceptable analytical goals. We conclude that most of the measured and derived bone-related biochemical variables in fasting plasma and urine are sufficiently reproducible in postmenopausal women to be useful for ranking individuals for a period up to 5 years.

Fracture risk is adversely related to bone density, wherever it is measured. Women should be screened by bone densitometry around the time of the menopause and treated with calcium or hormones if the density is low. Women with vertebral compression should be treated with calcitriol if calcium absorption is low, with hormones if urine calcium is high, and with calcitriol and hormones if both abnormalities are present. It is uncertain whether newer treatments offer any advantages over this regimen. Vitamin D is indicated in household individuals or others with low levels of 25 OHD to prevent loss from secondary hyperparathyroidism and perhaps also to improve muscle power.

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 critical examination of a meta-analysis of the effects of calcium supplements on heart attacks in five prospective trials on 8,016 men and women, and consideration of related publications by the same author.The meta-analysis was found to be subject to several limitations including non-adherence to the clinical protocol, multiple endpoint testing and failure to correctly adjust for endpoint ascertainment. The main risk factors for myocardial infarction were not available for 65% of the participants, and none of the trials had cardiovascular disease as its primary endpoint. There were more overweight participants, more subjects on thyroxine and more men on calcium than on placebo. In particular, over 65% of all the heart attacks were self-reported. When the evidence was considered in the light of Austin Bradford Hill's six main criteria for disease causation, it was found not to be biologically plausible or strong or to reflect a dose-response relationship or to be consistent or to reflect the relationship between the trends in calcium supplementation and heart attacks in the community or to have been confirmed by experiment. The addition of a more recent trial on 1,460 women over 5 years reduced the relative risk to 1.23 (P = 0.0695).Present evidence that calcium supplementation increases heart attacks is too weak to justify a change in prescribing habits.

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., it is the sodium load that influences urinary calcium rather than vice versa, but the converse may also occur, as after an oral calcium load or in hypercalcemia. When sodium is the determinant, 100 mmol of sodium takes out approximately 1 mmol of calcium in the urine. When calcium load is the determinant, each millimole of calcium appearing in the urine is associated with an extra 10-20 mmol of sodium. Sodium-dependent calcium loss may continue indefinitely, but calcium-dependent natriuresis is self-limiting. There is a significant correlation between calcium and sodium in fasting urine from both pre- and postmenopausal women, but there is more calcium relative to sodium in postmenopausal women than in premenopausal women. In postmenopausal but not premenopausal women, urinary hydroxyproline is also related to obligatory sodium and calcium output, and restriction of salt intake lowers not only urinary sodium but also calcium and hydroxyproline. There is not only an increase in obligatory calcium excretion at the menopause, but also an increase in the fasting urinary sodium, which in turn accounts for some of the increase in calcium output. This rise in fasting urinary sodium represents a delay in sodium excretion that may have a significant effect on calcium homeostasis.

Objective To evaluate the effects of short-term administration of chlorothiazide on fasting urinary hydroxyproline, an index of bone resorption, and other bone-related biochemical parameters in normal post-menopausal women. Design Subjects served as their own control before and after chlorothiazide treatment. Setting Subjects were recruited by advertisement. Participants Thirteen healthy post-menopausal women with a mean age of 65 years. Intervention Each subject was given chlorothiazide 500 mg bd po for 7 days. Fasting blood and urine samples were obtained immediately before the commencement of chlorothiazide (day 1) and 2 and 7 days after starting chlorothiazide. Results Chlorothiazide decreased the urinary calcium/creatinine (mean value day 1, 0.267; day 2, 0.143; day 7, 0.135; P < 0.001) and hydroxyproline/creatinine (day 1, 0.0192; day 2, 0.0145; day 7, 0.0139; P < 0.02) molar ratios. Conclusion Chlorothiazide decreases fasting urinary hydroxyproline, a marker of bone resorption in post-menopausal women. This observation supports a potential role for thiazide diuretics in the prevention of osteoporosis. The observed fall in urinary hydroxyproline is of the same order as that seen after treatment with estrogen or calcium supplements.

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.