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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.

The biochemical effects of a single oral dose of 10 mmol of calcium on certain blood and urine variables were studied in 20 elderly postmenopausal subjects (mean age 72.3±6.2 years) with a very low dietary calcium intake (mean 7.2±3 mmol/day). Twelve hours after calcium administration, the plasma total calcium, phosphate and bicarbonate, and the urinary calcium/creatinine ratio rose, while the plasma parathyroid hormone and chloride, and urinary hydroxyproline/creatinine and phosphate/creatinine ratios fell. These results show that a single oral dose of calcium suppresses bone resorption in elderly women with low dietary calcium intake, and that long-term supplementation may be important in the prevention of osteoporosisrelated fractures.

In 32 controlled trials of calcium supplementation (700-2000 mg) in 3,169 postmenopausal women, mean bone loss in the controls was -1.07% p.a. and in the treated subjects -0.27% p.a. (P for difference0.001). The effect was similar at all measured sites and at all doses of 700 mg or more but became weaker after 4 years.We have reviewed 32 trials of calcium supplementation in 3,169 postmenopausal women.We found 24 publications reporting 32 controlled trials lasting at least 1 year, which provided annual percentage changes in bone mass or density at one or more sites in the calcium-treated and control subjects.The median calcium supplement was 1,000 mg, median duration of the trials 2 years and total number of sites measured 79. The average of the mean rates of change in bone mass or density was -1.07% p.a. (P0.001) in the controls and -0.27% p.a. (ns) in the treated subjects (P for difference0.001). The effect of calcium was much the same at all measured sites (forearm/hand, proximal femur, spine, and total body and others). Supplements of less than 700 mg were not effective, but there was no significant beneficial effect of higher doses. There was significantly faster bone loss at total calcium intakes below 1,150 mg than on intakes over 1,350 mg. The effect of calcium appeared to be lost after 4 years of treatment.Calcium supplementation of about 1,000 mg daily has a significant preventive effect on bone loss in postmenopausal women for at least 4 years.

BrMedJ 1990;300:1056-60 In a recent review Kanis and Passmore concluded that there was no case for supplementation of the diet with calcium for the prevention or treatment of osteoporosis.1 We consider that present evidence, taken as a whole, points to a different conclusion. We consider the matter under five main headings: experimental calcium deficiency; human calcium requirements; the relation between calcium intake, bone mass, and bone loss; the relation between calcium and hip fracture; and the role of calcium in established osteoporosis.

We have estimated the relative contributions of age and menopause to forearm mineral density in 485 normal postmenopausal women up to age 75 yr. In 87 pairs matched for years since menopause, in which 1 member was below 61 yr and the other was 61 yr or older, the mean bone density was significantly lower in the older than in the younger subjects despite their identical years since menopause (P less than 0.001). Further analysis suggested a model for bone loss after the menopause which comprises a menopausal component of exponential type and an age-related component which is linear and starts in the mid-50s. According to this model, a 70-yr-old woman has lost 11% of her bone due to menopause and 18% as a function of age. Thereafter, the age-related function is dominant. Early menopause is associated with a self-limiting loss of bone which does not progress further until aging exerts its effect. The main conclusion is that the significance of early menopause as a risk factor for osteoporosis has been overstated.

Background. The possibility that monoaminergic neurotransmission is altered in pathological gambling was examined.Methods. Monoamines and their metabolites were measured in CSF obtained at level L4–5 from ten pathological gamblers and seven controls.Results. A decrease in dopamine and an increase in 3,4-dihydroxyphenylacetic acid and homovanilic acid was found. Noradrenaline and its metabolite 3-methoxy-4-hydroxyphenylglycol was also increased but 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were unchanged.Conclusion. It is suggested that the function of the dopaminergic system, possibly mediating positive and negative reward, and the noradrenergic system, possibly mediating selective attention, is changed in pathological gambling.

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 (500 mg doses at 9 a. m. and 9 p. m. each) reduced bone resorption markers during the day, but not during the night. We have now evaluated the effect of 1500 mg of calcium given as a divided dose of 500 mg in the morning and 1000 mg in the evening on bone resorption. We studied 26 healthy women (median age 56 years) whose menopause was less than five years before. On two 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. On the second day, 500 mg of calcium in the carbonate form was taken at 9 a. m. (at the start of the collection) and a further 1000 mg at 9 p. m. (at the start of the second night collection). Calcium supplementation decreased urinary deoxypyridinoline (DPyr/Cr) during the day (p = 0.08) and night (p < 0.05), as well as urinary pyridinoline (Pyr/Cr) both by day (p < 0.05) and night (p < 0.001). There were also decreases in urine hydroxyproline. We conclude that the acute administration of 500 mg of calcium in the morning and 1000 mg in the evening to early postmenopausal women suppresses bone resorption markers during both the day and night.

OBJECTIVE: To establish whether calcium-enriched milk reduces bone loss in women who are within five years of the menopause and have a basal calcium intake < or = 1,250 mg. DESIGN: Two-year open, crossover study. SETTING: A community-based study carried out in Adelaide, South Australia, between September 1997 and June 2000. PARTICIPANTS: 115 women recruited by newspaper advertisement, who were less than five years postmenopausal, were not taking hormone or other therapy that could affect bone and had a usual calcium intake < or = 1,250 mg daily. INTERVENTION: Participants were randomly allocated to Group 1 (who received a supplement of 3 L of calcium-fortified milk weekly in the first year) or Group 2 (who followed their usual diets in the first year). In the second year, Group 1 reverted to their usual diets, and Group 2 received the milk supplement. MAIN OUTCOME MEASURES: Difference in loss of bone mineral density (BMD) at the spine and forearm in the same individuals on and off the milk supplement; urinary excretion of bone resorption markers in a subset of 72 participants in the first year. RESULTS: With each woman serving as her own control, the rate of bone loss from the spine was 1.76 percentage points less when the women were taking the milk supplement than when they were on their usual diet (95% CI, 0.54%-2.98%; P=0.006). However, there was no significant difference in bone loss in the forearm. Fasting urine levels of two markers of bone resorption (hydroxyproline and deoxypyridinoline) were significantly lower in 36 women in the milk group than in 36 women in the usual-diet group (P=0.03 for both markers). CONCLUSION: Supplementing the diet with calcium-fortified milk early in the postmenopausal period delays bone loss at the spine but not at the forearm, and reduces the excretion of bone resorption markers.

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.

Postnatal depression refers to a non-psychotic depressive episode that begins in or extends into the postpartum period. The aims of this study were to examine the prevalence of depressive symptoms in a pregnant and later postnatal population, to determine the natural course of these symptoms and whether there is an association between antenatal and postnatal depressive symptomatology.A longitudinal study with a total population of 1,558 consecutively registered pregnant women in the southeast region of Sweden. Presence of depressive symptoms was measured with the Edinburgh Postnatal Depression Scale on four occasions namely in gestational week 35-36, in the maternity ward, 6-8 weeks and 6 months postpartum.The prevalence of depressive symptoms during late pregnancy was 17%; in the maternity ward 18%; 6-8 weeks postnatally 13%; and 6 months postnatally, 13%. A correlation between antenatal and postnatal depressive symptoms was found (r=0.50, p0.0001).Detection of women at risk for developing postnatal depressive symptoms can be done during late pregnancy. Antenatal care clinics constitute a natural and useful environment for recognition of women with depressive symptoms.

It must be a source of some surprise to rational scientists that the human requirement for calcium an apparently inoffensive nutrient that contributes so much to our physical stability arouses strong emotions in many breasts. Calcium requirements and allowances seem to attract more controversy and generate more heat than do the requirements and allowances for any other nutrient the latest example of this being a recent controversy in the columns of the New York Times. The problem may be that calcium turnover is too slow and the effects of deprivation and replenishment too gradual to be easily demonstrated in humans; perhaps it is the very efficacy of the calcium homeostatic system that makes this system difficult to study. Whereas plasma concentrations of other nutrients (eg sodium potassium phosphorus and magnesium) can be lowered relatively easily and quickly by experimental deprivation plasma (ionized) calcium is so well protected through access to the reserve stores in the skeleton that it cannot be used as a marker of calcium nutrition. Although there is overwhelming evidence that calcium deprivation causes osteoporosis in experimental animals it would be both immoral and impractical to try to reproduce such experiments in humans. The calcium requirement therefore must be estimated by indirect means that even if they satisfy many of the experts in the field are open to criticism by others. Nonetheless there is no smoke without fire and it may be that this controversy does reflect a deeper reality although not perhaps the one that the critics of the calcium story envisage. (excerpt)

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 concentration of 25(OH)D required for bone health.Our objective was to study the relations between serum PTH, serum vitamin D metabolites, and other calcium-related variables in postmenopausal women.This was a cross-sectional study of 496 postmenopausal women without vertebral fractures attending our menopausal osteoporosis clinics.PTH was significantly positively related to age and serum 1, 25-dihydroxyvitamin D ¿1,25(OH)(2)D and inversely related to 25(OH)D and plasma ionized calcium. There was a step-like increase in PTH as serum 25(OH)D fell below 40 nmol/L. In women with 25(OH)D concentrations40 nmol/L, 1,25(OH)(2)D was positively related to 25(OH)D; in women with 25(OH)D concentrations/=40 nmol/L, the relation was the inverse. In women with 25(OH)D concentrations/=40 nmol/L, 1,25(OH)(2)D was most closely related to PTH; in women with 25(OH)D concentrations40 nmol/L, 1,25(OH)(2)D was most closely (inversely) related to plasma creatinine. Therefore, with serum 25(OH)D concentrations increasingly40 nmol/L, serum 1,25(OH)(2)D becomes critically dependent on rising concentrations of PTH.The data suggest that aging women should maintain 25(OH)D concentrations40 nmol/L (which is the lower limit of our normal range for healthy young subjects) for optimal bone health.

This study was initiated in order to describe and evaluate the effects of a therapeutic drug monitoring (TDM) routine of selective serotonin reuptake inhibitors (SSRIs) on treatment strategies and drug costs in depressed elderly patients.Blood samples were drawn from elderly depressed patients and analysed for steady-state trough serum concentrations of citalopram (n = 48), paroxetine (n = 48) or sertraline (n = 39). A global efficacy evaluation was made at baseline and after 6-9 months. Antidepressant drug costs before and after TDM were estimated.Eight samples were excluded due to technical problems or noncompliance. In 65 of the 127 (51.2%) remaining cases, the treatment strategy was changed according to the TDM outcome, in most a reduction of the prescribed dose. Bioanalytical TDM costs included the antidepressant drug costs after TDM were reduced by 10.2%.The results support the utility of TDM in the search for the individual minimum effective SSRI dose in the elderly.

The range of fat corrected distal forearm mineral content (FMC) (at a site which comprises approximately 75% cortical and 25% trabecular bone) and the effect of aging on FMC were determined in normal premenopausal women. In 106 women (mean age 39; range 18-56) the mean FMC was 1.184 (SD 148) g/cm; fat correction increased this to 1.239 (SD 148) g/cm. There were significant correlations between fat corrected FMC and height, weight and BMI (r greater than 0.16; P less than 0.05). In 43 of these women (mean age 35; range 18-51) repeat measurements of FMC were performed. The last measurement was separated from the first by a mean time interval of 27 +/- 3 months. There was no significant change in uncorrected FMC (baseline 1.185 +/- 0.21 g/cm compared with their final measurement 1.182 +/- .020 g/cm; P = 0.51). Fat-corrected FMC (baseline 1.229 +/- .021 g/cm compared with 1.223 +/- .020 g/cm later) tended to decrease although this change was not significant (P = 0.06). Age ranked cusum analysis demonstrated a non-significant fat-corrected rate of change in FMC of -.3% yr in those over 35 years of age (P less than 0.10). This data suggests that if there is any distal forearm bone loss before the menopause it is negligible.

Dear Editors, As researchers whose work is referred to in support of the hypothesis that calcium causes hip fractures, we feel entitled to comment on the ‘review’ in a recent issue of your journal [1]. The article could perhaps be better labelled ‘for debate’, since it is certainly not an objective review of the subject but rather the presentation of an idiosyncratic opinion. The authors postulate that calcium therapy weakens the femoral neck by inhibiting its expansion, but their published data on hip status assessed by DXA BMD do not support their case nor is it supported by the abstract they quote. Furthermore, they do not report the effect of calcium on the femoral neck in their own study, which would be of great interest. Periosteal expansion occurs on all long bones [2] and is likely to occur at the femoral neck, but whether the process is suppressed by calcium, and if so whether that is of any significance, is another matter. They do not quote our RCT data on the forearm, which shows that calcium supplementation is associated with increased cortical thickness and increased calculated strength in bending at the proximal radius [3]. Nor do they quote Boonen’s metaanalysis [4], which showed a pooled RR of 1.10 (0.89– 1.36; NS) in patients on vitamin D alone in four RCTs on 9,083 patients. By contrast, the pooled RR was 0.82 (0.71– 0.94; P=0.0005) in six RCTs on 45,509 patients on vitamin D with calcium. How can they reconcile their hypothesis with this much larger meta-analysis, which clearly shows the benefit of calcium in hip fracture prevention? But above all, they do not make it clear that the hip fracture data, which they derive from their original paper [5] (17/732 hip fractures on calcium and 5/739 in controls), was the intention-to-treat analysis; in those who actually took the tablets, there were six hip fractures on calcium and two on placebo (NS). How can anyone build such a far-reaching claim on such small numbers? How did it get past the reviewers? We also question the use of the word ‘trend’ by Reid and co-authors in this and their previous paper [6]. They appear to use trend to mean an effect that does not even meet the conventional level of weak statistical significance (P 800 U/day) with calcium (at least 1,200 mg per day) reduces appendicular fractures of all kinds and thus should be the first intervention to reduce fracture risk in the elderly. Osteoporos Int (2009) 20:831–832 DOI 10.1007/s00198-008-0755-3

OBJECTIVE To investigate the role of serum 1,25-dihydroxyvitamin D (1,25D) in the decreased calcium absorption found in men with osteoporosis. DESIGN Prospective study of patients referred to a university teaching hospital clinic for investigation of possible osteoporosis. PATIENTS Male patients referred for investigation for osteoporosis, from 1981 to 1995, because of specific risk factors or radiological suspicion of osteoporosis. Men with vertebral compression fractures were compared with those without. MEASUREMENTS Height and weight, radiocalcium absorption, serum 1,25D and fasting urinary calcium and hydroxyproline excretion. RESULTS The men with vertebral fractures had higher fasting urinary hydroxyproline excretion (P = 0.003) and lower calcium absorption (P = 0.002) than the men without. Calcium absorption was positively related to 1,25D in both groups but the estimated calcium absorption at zero 1,25D was lower in the osteoporotic than the normal group. 1,25D was lower in the osteoporotic group than in the normal group. However this difference could only explain about half of the difference in calcium absorption between the groups. CONCLUSIONS Calcium absorption is low in men with osteoporosis. About half of the deficit is due to low serum 1,25-dihydroxy vitamin D levels but there appears, in addition, to be some intestinal resistance to its effect on calcium absorption.

Calcitriol is used in the treatment of osteoporosis but the indications for its use have not been clearly defined. Because it stimulates calcium absorption, we have tended to select osteoporotic patients with low calcium absorption for this therapy and now report the results. We measured the hourly fractional rate of calcium absorption (alpha) with 45Ca and fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OHPr/Cr) in 103 postmenopausal women aged 68 (0.67SE) years with vertebral compression fractures (77) or forearm or vertebral bone density below the young normal range (26). They were given 0.25 microg daily of calcitriol (Rocaltrol, Roche, Basle, Switzerland) with a 1 g calcium supplement daily for 6-12 weeks, when the biochemical tests were repeated. Initial OHPr/Cr was inversely related to initial alpha (P = 0.001) and positively to initial Ca/Cr (P < 0.001). alpha rose on therapy from 0.47 (0.018) to 0.59 (0.018) per hour (P < 0. 001) and OHPr/Cr fell in the whole group from 19.1 (0.83) to 13.8 (0. 58) (P < 0.001). The change in alpha on therapy (corrected for the "regression to the mean effect") was inversely related to initial alpha (P < 0.001) as was the change in OHPr/Cr (P = 0.001). There was no relationship, however, between initial Ca/Cr and either the rise in alpha or the fall in OHPr/Cr on therapy. The data support the concept that low calcium absorption is a cause of negative calcium balance in postmenopausal osteoporosis and that the effectiveness of calcitriol therapy is inversely related to the initial rate of calcium absorption.

The relations between calcium absorption, dietary calcium intake, 1,25-dihydroxyvitamin D 3 (calcitriol), and vitamin D receptor (VDR) gene polymorphisms were evaluated in 99 healthy women who were approaching menopause (mean age: 47 y, range: 43-53 y). Dietary calcium was assessed by food-frequency questionnaire and calcium absorption was measured by a single-isotope radiocalcium test. VDR alleles were classified according to the presence (b, t, a) or absence (B, T, A) ) of the BsmI, Taql, and ApaI restriction enzyme cutting sites. Radiocalcium absorption was positively related to serum calcitriol (r = 0.23, P < 0.05) and inversely related to dietary calcium intake (r = -0.26, P < 0.01). There was, however, no significant relation (r = 0.10) between serum calcitriol concentrations and dietary calcium. Radiocalcium absorption was higher in the bbaaTT haplotype (P < 0.05) and the aa genotype (P < 0.05), polymorphisms said to be associated with a higher bone density. We conclude that serum calcitriol and dietary calcium are independent determinants of calcium absorption in premenopausal women and that VDR gene polymorphisms influence calcium absorption.

Summary OBJECTIVE Little Is known about the pattern of age-related bone loss in men, and although androgens are required for optimum bone mass it Is not clear whether the fall in bone mass with age in men is related to failing androgens. DESIGN Cross-sectional measurement of bone density, at five sites, and markers of bone resorption and formation in 147 normal volunteers aged 20-83 years. SUBJECTS Healthy laboratory workers, hospital staff, their relatives, and husbands of women attending our osteoporosis clinic. MEASUREMENTS Forearm density (fat corrected), spine L2-L4, femoral neck, Ward's triangle and trochanter density; serum procollagen I C-terminal extension peptide, osteocalcin, bone alkaline phosphatase and collagen I C-terminal telopeptlde; fasting urine hydroxy-proline/creatinine, pyridinoline/creatinine and deoxy-pyridinoline/creatinine; and free androgen Index (FAI), measured as serum testosterone/sex hormone binding globulin. RESULTS Bone loss accelerated at most sites after age 50. There was a significant fall In FAI from the third decade onwards. The levels of ail bone markers fell with age. CONCLUSIONS Bone loss In men appears to accelerate from age 50 and is associated with decreased bone formation which may be associated with falling levels of free androgen.

There are few studies that focus on the interpersonal aspect of everyday ethical conflicts. Conceptual frameworks for research into ethical decision making in the health care system are mainly based on an ethic in which objectivity and principle-based thinking is emphasized, leaving the experience of concrete moral conflicts relatively unexplored. The aim of this paper is to analyze the dimensions of "moral sensing," a concept identified in an earlier grounded theory study of psychiatric nursing. Four dimensions of the concept of moral sensing, i.e., feeling, intuition, benevolence and genuineness, were synthesized by reviewing the works of past and contemporary philosophers. The analysis of moral sensing and its dimensions is exemplified by actual nurse-patient encounters in psychiatric nursing practice.

Calcium supplementation decreases bone re- sorption and retards bone loss in women. There is little infor- mation about the effects of calcium supplementation in men. The effects of a l-g oral calcium load at 0900 on bone-related bio- chemical variables were evaluated in 13 normal men (aged S 1- 70 y). Calcium administration was associated with increases in plasma ionized calcium (P < 0.001) and urinary calcium (P < 0.001), and a decrease in plasma parathyroid hormone (P < 0.001). There was a nonsignificant trend (r = -0.47, P = 0. 1 1) for the decrease in plasma parathyroid hormone to be related to radiocalcium absorption. After the calcium load there were decreases in the urinary hydroxyprohine-creatinine ratio from 1 1 ± 1.1 to 7.9 ± 0.6 (P < 0.01), the urinary deoxypyri- dinohine-creatinine ratio from 14.0 ± 1.8 to 10.1 ± 0.9 (P < 0.05), and the urinary pyridinoline-creatinine ratio from 52 ± S to 40 ± 3 (P < 0.01) between baseline and 6 h. There was no change in plasma osteocalcin. These observations indicate that a l-g calcium load suppresses biochemical markers of bone re- sorption for � 6 h in normal men and support the concept that calcium supplementation may be useful in the prevention of bone loss in men. Am J Clin Nutr 1994;60:965-8.

BACKGROUND Urine calcium after an overnight fast is higher in osteoporotic than in normal post-menopausal women. The question is whether this is the cause or effect of the bone-losing state. OBJECTIVE To establish whether the elevated obligatory calcium loss in osteoporotic women is due to a raised filtered load of calcium or to reduced renal tubular reabsorption of calcium. DESIGN Covariance analysis using total plasma calcium and its fractions as the covariates. PATIENTS Eighty-two untreated post-menopausal women without vertebral compression and 137 untreated post-menopausal with vertebral compression all between the ages of 61 and 75 years. MEASUREMENTS After an overnight fast, calcium, albumin, globulins, anion gap and bicarbonate were measured in the plasma, and calcium, sodium and creatinine in the urine. The calcium fractions in plasma and the calcium/creatinine and sodium/creatinine ratios in urine were calculated. Bone density was measured in the distal forearm. RESULTS The ultrafiltrable and ionized calcium in the plasma and the calcium/creatinine ratio in the urine were significantly higher in the women with vertebral compression than in those without. On covariance analysis, neither total plasma calcium nor any of the plasma calcium fractions made a significant contribution to the difference in fasting urine calcium between normal and osteoporotic women, whether bone status was defined by vertebral compression or by bone density. CONCLUSIONS The increased obligatory calcium loss in osteoporotic women is not due to an increase in the filtered load of calcium and must therefore reflect reduced renal tubular reabsorption. This implies that the calcium loss in the urine is not the result of increased bone resorption but is more likely to be causal.

Suicide risk after attempted suicide, as predicted by cerebrospinal fluid (CSF) monoamine metabolite concentrations, was studied in a sample of 92 psychiatric mood disorder inpatients admitted shortly after attempting suicide. The potential of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the CSF to predict suicide risk within the first year after attempted suicide was studied by means of survival analysis after after median split subgrouping. Eleven patients (12%) committed suicide within 1 year after attempted suicide. Eight of these belonged to the below-the-median (87 nM) CSF 5-HIAA subgroup, that is, the suicide risk was 17% as compared with 7% among those with above-the-median CSF 5-HIAA. The cumulative number of survived patient-months during the first year after attempted suicide was significantly lower in the low CSF 5-HIAA subgroup. It was concluded that low CSF 5-HIAA predicts short-range suicide risk after attempted suicide in mood disorder psychiatric inpatients. These findings lend further support to the serotonin hypothesis of suicide risk.

Oral calcium loading is known to decrease parathyroid hormone levels in primary hyperparathyroidism. We have examined the effects of a calcium supplement on bone resorption in postmenopausal primary hyperparathyroidism. Fasting blood and urine samples were obtained in 12 postmenopausal women (median age 64 yr) with primary hyperparathyroidism associated with mild hypercalcemia (plasma calcium < 3.00 mmol/l). Further samples were obtained 12 hours after a 1 g calcium supplement given at 2100 h. After calcium administration there were rises in plasma ionized calcium (p < 0.02), plasma phosphate (p < 0.05) and the renal tubular maximum reabsorption capacity for phosphate (p < 0.01) and falls in parathyroid hormone (p < 0.05) and the renal tubular maximum reabsorption capacity for calcium (p < 0.05). The urinary calcium/creatinine increased (p < 0.01) and the urinary hydroxyproline/creatinine (p < 0.02) fell. These results indicate that calcium loading inhibits bone resorption in postmenopausal women with mild primary hyperparathyroidism.

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 …

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 which the observations were made and in the preceding 2 mo. Serum 25(OH)D was positively related to hours of sunlight (with a time lag of 2 mo) and to skin thickness, and negatively to body mass index (wt/ht2). Serum 25(OH)D fell significantly after age 69 y. Seasonal variation of serum 25(OH)D was greater in lean than in fat subjects, which we attributed to the larger fat mass and consequent larger pool size in the latter group. The results suggest that the tendency for serum 25(OH)D to fall with age is due in part to the age-related decline in skin thickness.

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. DESIGN/PATIENTS The effects of treatment with norethisterone (5 mg/day) on bone related biochemical variables was determined in 44 women with post-menopausal osteoporosis. The effects of norethisterone on forearm bone mineral content (FMC) were evaluated by serial measurements in 39 of these women. MEASUREMENTS We measured forearm mineral content, forearm mineral density, forearm fat content and fat-corrected forearm mineral density. Biochemical measurements included plasma calcium and plasma calcium fractions (ionized, protein bound, complexed and ultrafiltrable), alkaline phosphatase, bicarbonate, phosphate, albumin and globulins, serum parathyroid hormone, osteocalcin and 1,25-dihydroxyvitamin D, radiocalcium (45Ca) absorption and fasting urinary calcium/creatinine, sodium/creatinine, phosphate/creatinine and hydroxyproline/creatinine molar ratios. RESULTS After 4 months of treatment norethisterone produced a fall in plasma calcium (mean +/- SEM from 2.40 +/- 0.14 to 2.32 +/- 0.13 mmol/l, P < 0.001), primarily in the non-ionized calcium, due to a decrease in plasma bicarbonate (from 29 +/- 0.28 to 27 +/- 0.28 mmol/l, P < 0.001). There were decreases in urinary calcium/creatinine (from 0.41 +/- 0.03 to 0.19 +/- 0.02, P < 0.01) and sodium/creatinine (from 15 +/- 1.1 to 10 +/- 0.93, P < 0.001) molar ratios and a rise in the renal tubular maximum for calcium reabsorption (TmCa) (from 2.36 +/- 0.041 to 2.55 +/- 0.059 mmol/l of glomerular filtrate, P < 0.001). Plasma phosphate, urinary phosphate/creatinine and tubular maximum for phosphate reabsorption (TMP) all fell (P < 0.01). Both the urinary hydroxyproline/creatinine (P < 0.001) and plasma alkaline phosphatase (P < 0.001) fell. Serum parathyroid hormone rose from 4.1 +/- 0.36 to 5.5 +/- 0.51 pmol/l (P < 0.02) and radiocalcium absorption increased from 0.67 +/- 0.08 to 0.81 +/- 0.10 fx/h (P < 0.01). There was no change in serum 1,25-dihydroxy vitamin D. After treatment with norethisterone for 4 months there was an increase in forearm bone mineral content (P < 0.05) and a decrease in forearm fat content (P < 0.02). After two years treatment with norethisterone fat-corrected forearm bone mineral content rose (mean change 17.0 +/- 5.5 mg/cm, P < 0.01). CONCLUSIONS These results suggest that norethisterone prevents bone loss in post-menopausal osteoporosis by decreasing bone turnover, has a vitamin-D independent effect on intestinal calcium absorption, and increases serum parathyroid hormone levels.

The relationships between metacarpal morphometric, vertebral and forearm density measurements and the prevalence of vertebral and peripheral fractures were examined in 239 postmenopausal women (median age 63, range 32-84 years). Metacarpal cortical area/total area ratio (CA/TA) was measured with needle calipers, forearm mineral density (FMD) by single photon absorptiometry and vertebral mineral density (VMD) by single energy quantitative computed tomography. Of the 239 subjects 97 had not suffered any fractures, 44 had at least one previous vertebral fracture but no peripheral fractures, 41 had a history of peripheral fracture but no vertebral fracture and 57 had suffered both peripheral and vertebral fractures. There were significant correlations between a single measurement of CA/TA and both FMD (r = 0.65, p < 0.001) and VMD (r = 0.41, p < 0.001). Similar correlations existed between the mean of multiple measurements of CA/TA and both FMD and VMD. CA/TA (p < 0.001), FMD (p < 0.001) and VMD (p < 0.001) were reduced in subjects who had suffered fractures, when compared with the no fracture group. The percentage of cases in each of the four fracture groups (vertebral fracture only, peripheral fracture only, peripheral and vertebral fracture, peripheral or vertebral fracture) misclassified with reference to the no fracture group were similar with CA/TA, FMD or VMD measurements. We suggest that metacarpal morphometry, which is widely available at relatively low cost, yields cross-sectional information about bone density and fracture risk, comparable with that obtained by forearm and vertebral densitometry.

STUDY OBJECTIVE--The aim was to estimate fracture rates and fracture prevalence from fracture histories in normal postmenopausal women. DESIGN--Apparently healthy postmenopausal women were recruited by advertising in the media. Fracture histories were obtained by personal interview in 1983 and again by interview or questionnaire in 1988. Fracture rates were calculated prospectively and retrospectively. PARTICIPANTS--492 women (mean age 58.6 years) were selected from over 1000 applicants on the basis that they were suffering from no disease nor taking any therapy which might affect their bones. MEASUREMENTS AND MAIN RESULTS--Retrospective premenopausal and postmenopausal fracture rates were calculated in 1983, prospective rates calculated from 1983 to 1988, and retrospective rates checked again on the second occasion. The retrospective and prospective fracture rates were very similar. The five year fracture rates were low and steady until the menopause, when they rose by a factor of 10 and reached a new plateau after about 15 years. The results were comparable to those obtained from hospital statistics. CONCLUSIONS--The menopausal rise in fracture rates not only involves wrist fractures but most peripheral fractures, and probably reflects postmenopausal loss of trabecular bone. Meaningful fracture rates can be calculated from individual fracture histories in a well defined population. This technique may be particularly useful in developing countries where public health data may be incomplete.

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, 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.

We have measured calcium, albumin, globulin, bicarbonate, and anion gap in the plasma; and calcium, sodium, and creatinine in the urine, in 115 premenopausal and 140 postmenopausal normal women after an overnight fast, and calculated the calcium fractions in the plasma and the calcium/and sodium/creatinine ratios in the urine. The total ultrafiltrable calcium was significantly higher in the postmenopausal group, mainly due to their higher complexed calcium fraction, due in turn to their higher bicarbonate and anion gap concentrations. Urinary calcium was also significantly higher in the postmenopausal group even after correcting for sodium. After matching for total calcium and each of the calcium fractions in turn, the urinary calcium remained significantly higher in the post- than in the premenopausal sets even after correction for sodium. The implication is that the rise in urinary calcium at the menopause is due to reduced tubular reabsorption of calcium rather than to an increase in filtered load. We suggest that estrogens promote tubular reabsorption of calcium and that the rise in bone resorption at the menopause could be accounted for, at least in part, by the effect of estrogen deficiency on the kidney.

Female Sprague-Dawley rats (n = 72), 6 months old, underwent either sham operation, oophorectomy, adrenalectomy, or combined oophorectomy and adrenalectomy (OA). They were all maintained on normal saline ad libitum and 20 g/day 1.1% calcium chow. Nine weeks after operation, the trabecular bone volume of the distal femoral shaft was significantly lower (P less than 0.001) in the adrenalectomized (11.1%), oophorectomized (7.0%), and OA (8.3%) animals than in sham-operated animals (19.8%). Eighteen weeks after operation, the trabecular bone volume in OA animals had fallen to a mean of 3.8% (sham 17.0%), and the length of the femur had increased to 38.8 mm after OA (sham 36.8 mm, P less than 0.01). OA animals treated with 0.35 mg/kg/week nandrolone decanoate from 9 weeks postoperatively onward, had twice the femoral trabecular bone volume of untreated animals at 18 weeks (P less than 0.05). By contrast, no significant differences were found in vertebral body trabecular bone between any groups, including groups receiving treatment with androgens. We have found that, by 9 weeks after operation, adrenalectomy alone causes significant loss of metaphyseal trabecular bone, similar to the progressive loss seen after oophorectomy.