Preventing osteoporosis naturally.
Explore the source record for details and available documents.
Bone Density↗
Biomedical subjects
R L Prince
Publications and source records attributed to R L Prince.
Predictors of low bone density in young adolescent females with anorexia nervosa and other dieting disorders.
OBJECTIVE: To compare the bone density of adolescent patients with anorexia nervosa with adolescent patients with other dieting disorders and to evaluate risk factors for low bone density in these patients. METHOD: Sixty-nine consecutive female patients referred to an adolescent eating disorders clinic were studied by interview, blood sampling, body composition, and lumbar spine bone density measurement using dual energy X-ray absorptiometry. RESULTS: Although patients with anorexia nervosa were more malnourished, their bone density was similar to other dieting patients. Patients were divided into a low and normal bone density group irrespective of psychiatric diagnosis. Patients with low bone density had dieted for longer, had lower lean body mass, more often had not achieved menarche, and had longer duration of secondary amenorrhea and lower estrogen levels. DISCUSSION: Irrespective of clinical diagnosis, adolescents with dieting disorders have increased risk of low bone density when malnutrition commences early in puberty and is associated with reduced lean body mass and impaired ovarian function.
Adolescent↗
Lifetime and five-year age-specific risks of first and subsequent osteoporotic fractures in postmenopausal women.
We examined the incidence of fragility fractures in Australian women 50 years of age and over using a Markov process with Monte Carlo simulations. The lifetime risks and the risks of sustaining first and subsequent clinically diagnosed fractures at osteoporotic sites were estimated according to age, nursing home entry and mortality rates. Hip and spine fractures were evaluated individually and fractures of humerus, forearm, wrist, ribs, pelvis, upper leg (excluding proximal femur) and tibia/fibula were considered in combination. The model predicted that 42.1% of women aged 50 years will sustain at least one fracture in their remaining lifetime, of whom half are expected to sustain multiple fractures. The lifetime risks of sustaining hip, clinical spine and other fractures were 17.0%, 9.6% and 30.4%, with the risks of multiple fractures at these sites estimated at 19.5%, 39.7% and 35.7% respectively. The proportion of women expected to sustain their first fracture increased from 1.9% of the population under 55 years of age up to 49.1% of women over 89 years of age. The 5-year age-specific risks of sustaining any subsequent fractures increased from 2.8% of women under the age of 55 years to 61.6% for women age 89 years and over. The increased risks of new fractures following a first fracture lead to a considerable burden of multiple fractures.
Age Factors↗
How to diagnose the presence of osteoporosis and assess the risk of fracture.
The approach to the diagnosis of osteoporosis has undergone a radical change in recent years. Osteoporosis is defined as a state of microarchitectural deterioration of the skeleton predisposing that skeleton to fragility fracture. In this sense it is a risk factor for disease in the same way as hypertension is a risk factor. Previously it was considered that bone density measurements using X-ray technology was the best non-invasive method of measuring the microarchitectural deterioration which thus came to define the disease. With the advent of new technology and a more logical approach to risk evaluation this simple approach is no longer appropriate. This chapter takes a stepwise approach to assessing the likelihood of osteoporosis on the basis of clinical factors and then suggests a method of integrating this information with a bone density measure to achieve a prediction of future fracture probability. Methods of diagnosing the cause of the osteoporosis are also outlined. Finally, application of these techniques in clinical care is discussed.
Aged↗
Regulation of the 1b isoform of the plasma membrane calcium pump by 1,25-dihydroxyvitamin D3 in rat osteoblast-like cells.
The first isogene of the plasma membrane calcium pump (PMCA1) is expressed on the apical plasma membrane of osteoblasts, but its regulation by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has not been studied in this cell type. We studied 1,25(OH)2D3 effects on PMCA1 function, protein, messenger RNA (mRNA), and isoform expression in osteoblasts. Of seven rat and human immortalized osteoblast-like cell lines studied, PMCA1 mRNA expression was confirmed in all. Only ROS 17/2.8 cells expressed measurable PMCA1 protein by Western analysis. Immunocytochemistry indicated that PMCA1 was expressed predominantly on the plasma membrane of ROS 17/2.8 cells. The 1,25(OH)2D3 but not 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] treatment of confluent ROS 17/2.8 cells resulted in an approximate 3- to 5-fold dose-dependent increase in PMCA1 expression of message and protein as assessed by Western and Northern analysis and vesicular 45Ca uptake of membrane vesicles. 1,25(OH)2D3 had no effect on PMCA1 posttranscriptional splicing. The 1b isoform of PMCA was expressed under all experimental conditions. 1,25(OH)2D3 favored increased expression of the 5.5 kilobases (kb) over the 7.5-kb PMCA1b transcript, with a 2-fold proportional increase in the smaller transcript relative to the larger transcript evident at the highest dose of 1,25(OH)2D3 studied. The resultant proportional increase in the smaller 5.5-kb transcript may increase mRNA stability and account for the increase in PMCA1b protein and function with 1,25(OH)2D3. These data provide evidence for the role of 1,25(OH)2D3 and PMCA1b in the regulation of calcium transport in bone cells.
24,25-Dihydroxyvitamin D 3↗
What strategies can women use to optimise bone health at this stage of life?
Dairy foods provide the major, readily absorbed sources of calcium. Women aged 40 years and over should consume 3-4 serves of low-fat dairy food per day. If calcium supplements are required, the best absorption rate is from a dose of 500-600 mg of calcium once or twice daily. Exercise, alone or in combination with other therapeutic interventions, is effective in preventing bone loss. Vitamin D supplements may be necessary for women with inadequate sun exposure. Salty foods and the addition of salt to food should be avoided. While there is emerging evidence for the role of phytoestrogens in bone health, more human trials are required to strengthen this evidence.
Adult↗
The promoter region of the human PMCA1 gene mediates transcriptional downregulation by 1,25-dihydroxyvitamin D(3).
The gene for plasma membrane calcium pump isoform1 (PMCA1) is expressed in calcium-transporting epithelia and bone mesenchymal cells and is upregulated to 1,25-(OH)(2)D(3) in those tissues. A candidate sequence for a vitamin D response element (VDRE) is present within a 1.7-kb promoter region of the human PMCA1 (hPMCA1) gene. We studied hPMCA1 promoter activity in MDBK and ROS 17/2.8 cell lines as PMCA1 mRNA expression is upregulated by 1,25-(OH)(2)D(3) in both. Structural analysis of the putative hPMCA1 VDRE sequence was performed using mobility shift analysis (EMSA) and nuclear extracts from COS-1 cells expressing human VDR (hVDR) and RXRalpha (hRXRalpha). 1,25-(OH)(2)D(3) induced transrepression of the entire 1.7-kb hPMCA1 promoter and of one promoter deletion construct in ROS 17/2.8 cells but not MDBK cells when assayed by luciferase reporter gene assays. Three additional hPMCA1 promoter deletion constructs were unaffected by 1,25-(OH)(2)D(3) in either cell line. While hVDR and hRXRalpha were capable of complexing with a rat osteocalcin DR3 VDRE, EMSA analysis of the potential VDRE from the hPMCA1 gene did not show interaction of either nuclear receptor. Our results indicate tissue-specific sensitivity of the promoter region of the hPMCA1 gene to direct transcriptional downregulation by 1,25-(OH)(2)D(3) and suggest that any positive regulatory VDRE must lie outside of the 1.7-kb core promoter.
Animals↗
Calcitriol upregulates expression and activity of the 1b isoform of the plasma membrane calcium pump in immortalized distal kidney tubular cells.
The plasma membrane calcium pump (PMCA) is ubiquitously expressed in calcium transporting epithelia. PMCA is encoded by four distinct genes (PMCA1-4) which can be further posttranscriptionally modified. PMCA1b is the only isoform of PMCA1 expressed in kidney and intestine. Calcitriol upregulates PMCA protein expression and activity and PMCA1 mRNA expression in the intestine. Calcitriol has a similar effect on kidney distal tubule PMCA activity in vivo but the cellular basis for this effect has not been studied. PMCA expression in Madin-Darby bovine kidney (MDBK) cells, a distal kidney tubule cell line, was compared with a proximal tubule (LLC-PK1) and embryonic (HEK 293) kidney cell line. Only MDBK cells express PMCA1b mRNA and PMCA protein. In MDBK cells, calcitriol increased steady state expression of PMCA1b mRNA and protein and upregulated the functional activity of PMCA on calcium transport to a similar degree. Furthermore, calcitriol enhanced PMCA1b mRNA stability. These data are consistent with in vivo localization studies demonstrating the distal kidney tubule localization of PMCA protein. Furthermore, they indicate that calcitriol is an important regulator of PMCA activity in the kidney distal tubule by a pathway that includes translation and posttranscriptional modification of PMCA1b.
Animals↗
Calcium absorption in postmenopausal osteoporosis: benefit of HRT plus calcitriol, but not HRT alone, in both malabsorbers and normal absorbers.
In a randomized trial involving 71 postmenopausal osteoporotic women with vertebral compression fractures, radiocalcium absorption studies using the (45)Ca single isotope method (alpha) were performed at baseline and after 8 months of treatment with either continuous combined hormone replacement therapy (HRT, as piperazine estrone sulfate 0.625-0.937 mg daily +/- medroxyprogesterone acetate 2.5 mg daily depending on uterine status) or HRT plus calcitriol 0. 25 microg twice daily. A calcium supplement of 600 mg nocte was given to only those women who had a daily calcium intake of less than 1 g per day at baseline, as assessed by recalled dietary intake. There was a significant decrease [0.74 (+/- 0.35 SD) to 0.58 (+/- 0. 22), Dalpha = -0.17 (+/- 0.26), p<0.0005] in alpha at 8 months compared with baseline in the HRT-treated group, but a significant increase [0.68 (+/- 0.31) to 0.84 (+/- 0.27), Dalpha = +0.16 (+/- 0. 30), p<0.003] in the HRT-plus-calcitriol treated patients, resulting in alpha being significantly higher after 8 months in the latter group than in the HRT-only group. Although 72% of the patients had been supplemented with calcium between the first and second studies, separate analyses revealed that the change in calcium intake had not affected the result. Further breakdown of the groups into baseline 'normal' absorbers (alpha >/=0.55) and 'malabsorbers' (alpha <0.55) revealed that alpha decreased with HRT treatment only in the normal absorbers, and remained stable in the malabsorbers. Conversely, following HRT plus calcitriol treatment, alpha increased only in the malabsorbers, the normal absorbers in this group remaining unchanged. In conclusion, our data show that HRT, of the type and dose used in this study, did not produce an increase in absorption efficiency; it was in fact associated with a fall. Increased absorption efficiency cannot be achieved unless calcitriol is used concurrently, and then only in patients with malabsorption. Calcitriol also had a significant effect in normal absorbers in that it prevented the decline in alpha seen with HRT alone, and thus should be considered in all patients with postmenopausal osteoporosis treated with HRT.
Aged↗
Diagnosing osteoporosis: the value of quantitative ultrasound.
Explore the source record for details and available documents.
Absorptiometry, Photon↗
Paget's disease: acquired resistance to one aminobisphosphonate with retained response to another.
Twenty-five years after the first paper on etidronate in Paget's disease, there are few published papers that address bisphosphonate resistance as a specific clinical phenomenon. We report our data from two studies. Study 1 is a retrospective study of 20 patients with moderate to severe disease who were treated with intravenous (iv) pamidronate (221 +/- 18 mg [SEM]; range 60-360 mg), and after biochemical remission and relapse were retreated with generally larger iv dosage (293 +/- 28 mg; range 180-600 mg). The nadir bone turnover values were similar: plasma alkaline phosphatase (pAP) in 20 patients was 243 +/- 40 IU/l (mean +/- SEM) after the first course, and 267 +/- 44 IU/l after the second (reference range [RR] 35-135 IU/l). Likewise, fasting urinary hydroxyproline excretion (HypE) in 14 of the 20 patients was 4.5 +/- 1.1 micromol/LGF and 4.1 +/- 0.9 micromol/LGF, respectively (RR 0.40-1.92 micromol/LGF). However the minimum duration of biochemical remission was significantly shorter after the second course-10.9 +/- 1.7 months (first) and 5.6 +/- 0.9 months (second) (p < 0.03; Friedman's ANOVA n = 17). A subgroup of 10 patients who were followed for three courses showed a significantly higher pAP nadir in the third course. Study 2 is a prospective study of 40 patients, 23 previously untreated (NILPREV) and 17 previously treated with iv pamidronate (PAMPREV) and in biochemical relapse, who were randomly allocated to either oral alendronate 40 mg daily in 3 month units, or iv pamidronate 60 mg every 3 months. Treatment was continued until pAP and fasting urinary deoxypyridinoline/creatinine (Dpy/Cr) ratios (RR 5-27 micromol/mol) were both in the reference range, or a clear plateau in each marker developed. At baseline, there were no significant differences in either marker between the two NILPREV groups and between the two PAMPREV groups. Using log-transformed data, in NILPREV the pAP reductions were significant and similar over the first 6 months. However, although each Dpy/Cr reduction was also significant, the difference in responses favored alendronate (p < 0.015). In PAMPREV both markers showed no significant response to pamidronate; comparison showed a significantly greater response to alendronate (pAP p < 0.02; Dpy/Cr p < 0.002). Using two-way ANOVA, the pAP responses to alendronate in NILPREV and PAMPREV were similar and those to pamidronate were different (p = 0.034). The percentage of patients with both markers in the RR at 6 months or earlier were identical in NILPREV patients: alendronate 87% and pamidronate 87%. However in PAMPREV they were different: alendronate 83% and pamidronate 0% (p = 0.003). These data indicate: 1) patients treated with the same aminobisphosphonates for two courses show similar nadir values of bone turnover markers but a shorter remission time after the second course. In a third course the nadirs are significantly higher; and 2) in the alendronate/pamidronate comparison, NILPREV and PAMPREV patients showed similar pAP responses to alendronate, but significantly different responses to pamidronate. Thus, patients showing acquired partial resistance to one aminobisphosphonate (usually after two or more previous courses) are still capable of remission after exposure to another compound of the same class.
Aged↗
A case-control study of quality of life and functional impairment in women with long-standing vertebral osteoporotic fracture.
There have been several studies of the impact of vertebral osteoporotic fracture on the quality of life and functionality of individual subjects. To date, however, no direct comparisons with age-matched normal subjects without vertebral fracture have been made. The radiographs of 145 female clinic patients with vertebral fractures were reviewed by the study physicians. The controls were recruited from the electoral role and by media appeal. One hundred and sixty-seven women had radiographs taken to determine those without vertebral fracture. Fracture subjects and controls had to be ambulant and were excluded if they had significant radiologic evidence of degenerative disk or joint disease of the spine. One hundred cases and one hundred controls were matched by 5-year age groups. The number, position and severity of the vertebral fracture on the lateral radiographs of the cases was recorded. Quality of life was measured using the Short Form-36 (SF-36) (maximum score 100) and a utility score calculated from these results (maximum score 1). Two measurements of functionality were employed: the Modified Barthel Index (MBI) to assess the activities of daily living (maximum score 100) and the Timed 'Up & Go' (TUG) that measured the time taken for the subject to rise from sitting in a chair, walk 3 m along a line, return to the chair and sit down. The fracture subjects had 2.9 +/- 1.6 (mean +/- SD) vertebral fractures and the time since last fracture was 5.1 +/- 4.8 years. The SF-36 physical function component summary index results were: fracture subjects 36 +/- 11, controls 48 +/- 9 (p < 0.001). The SF-36 mental health component summary index results were: fracture subjects 50 +/- 11, controls 54 +/- 8 (p < 0.05). The utility scores were: fracture subjects 0.64 +/- 0.08, controls 0.72 +/- 0.07 (p < 0.001). The MBI results were: fracture subjects 97 +/- 5, controls 99 +/- 1 (p < 0.01). The TUG results were: fracture subjects 13.8 +/- 7.3 s, controls 10.1 +/- 4.1 s (p < 0.01). TUG and MBI scores correlated well with SF-36 scores; however, no domain of the SF-36 or functional measure correlated with either the number of vertebral fractures or the time since last vertebral fracture. Thus, clinically reported vertebral fractures impair both the quality of life and functionality of these subjects. The adverse impact of vertebral fracture on quality of life and functionality needs to be recognized by medical practitioners, subjects and the community, so that adequate health resources can be devoted to the prevention and treatment of this debilitating condition condition.
Aged↗
The effect of estrogen deficiency on calcium balance in mature rats.
The role of estrogen in the regulation of calcium balance is still poorly understood. A calcium balance study was performed to examine the effects of estrogen status in relation to fecal calcium loss as a component of bone loss after oophorectomy (OOX) in the mature rat. The components of the classic calcium balance were compared with calcium balance estimates obtained from whole body bone density. Six month or older Sprague Dawley rats were allocated to either a sham-operated or OOX group and fed a 0.1% calcium diet. The bone mineral density (BMD) and bone mineral content (BMC) were measured at baseline, 6 weeks, and 9 weeks. A calcium balance was done for 6 days before and 6 weeks post OOX. The fall in BMD from baseline to 9 weeks in the OOX group was significantly greater than in the sham-operated group. The calcium balance was more negative at baseline than at 6 weeks in both groups of animals because they had not adapted to the low calcium diet. However, the increase in calcium balance was significantly less in the OOX animals than in the sham-operated animals. The greater the rise in calcium balance from the baseline to the 6 weeks balance the less the fall in the calcium content of the whole body (Spearman correlation: r = 0.604 P = 0.008). The fall in fecal calcium, but not urine calcium or calcium consumed, was negatively correlated with the change in whole body BMC (Spearman correlation: fecal calcium r = -0.763 P = 0.001). Thus, the primary effect of estrogen deficiency on calcium balance in the mature rat appears to be calcium flux in the bowel, rather than renal calcium handling.
Animals↗
Prevention of appendicular bone loss in Paget's disease following treatment with intravenous pamidronate disodium.
It has been shown previously that intravenous pamidronate treatment for severe Paget's disease is associated with appendicular bone loss. This 2 year study was designed to determine whether cotreatment with calcitriol and a calcium supplement would prevent this. Intravenous pamidronate was used to treat 49 patients with symptomatic Paget's disease. Patients were stratified into two groups of differing biochemical severity based on hydroxyproline excretion (HypE) expressed as micromoles per liter of glomerular filtrate (GF): (1) a severe group with HypE > 10 micromol/L GF; and (2) a moderate group with HypE 5-10 micromol/L GF. Within each group, patients were randomly allocated to receive supplements of calcium and calcitriol (supplemented) or no supplements (unsupplemented) after initiation of pamidronate therapy. The severe group received 360 mg of pamidronate as six doses of 60 mg once weekly and the moderate group received 240 mg as four weekly doses of 60 mg. Patients were followed for 24 months following treatment and had serial bone densitometry of the forearm measured as well as urine and plasma biochemistry. When the groups were combined, the unsupplemented patients showed a decrease in bone mineral density (BMD) at the ultradistal forearm site, which persisted to 24 months. Those supplemented with calcium and calcitriol showed an increase in BMD and the difference between the two groups was significant at all times posttreatment (p < 0.03). When the groups were analyzed separately, those with moderate disease again showed significant differences in BMD between supplemented and unsupplemented patients at all timepoints. In the severe group, the differences did not reach statistical significance due to smaller patient numbers. Similar changes in BMD were also observed at the forearm shaft site. When serial parathyroid hormone (PTH) levels (with the moderate and severe groups combined) were plotted against time since treatment the rise in PTH in the supplemented patients was less than the rise in the unsupplemented patients (p < 0.04). These results suggest that forearm bone loss after intravenous pamidronate treatment for moderate-to-severe Paget's disease can largely be prevented by administration of calcium and calcitriol. The mechanism may be a blunting of the secondary hyperparathyroidism that occurs after intravenous pamidronate. These findings may have wider application in moderate-to-severe Paget's disease treated with other bisphosphonates.
Administration, Oral↗
Osteoporosis detection and treatment.
Explore the source record for details and available documents.
Aged↗
Hypovitaminosis D in medical inpatients.
BACKGROUND: Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown. METHODS: We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward. RESULTS: A total of 164 patients (57 percent) were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, < or = 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-nine percent of the patients who consumed less than the recommended daily allowance of vitamin D and 43 percent of the patients with vitamin D intakes above the recommended daily allowance were vitamin D-deficient. Inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent. CONCLUSIONS: Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency.
Adolescent↗
Effects of zinc and other nutritional factors on insulin-like growth factor I and insulin-like growth factor binding proteins in postmenopausal women.
Insulin-like growth factor I (IGF-I) is a critical factor in the regulation of various physiologic effects, including bone formation and protein metabolism. Nutrient intake is a main regulator of circulating IGF-I. The relation of zinc status and IGF-I in adulthood has not been studied adequately even though suboptimal intakes of zinc are reported widely in the elderly. This study examined the relation between calculated nutrient intakes from 119 postmenopausal women and concentrations of IGF-I and IGF binding proteins (IGFBPs). Dietary intake was evaluated by 4-d weighed diet records at baseline and 2 y. Mean intakes of 25 nutrients were calculated. Concentrations of IGF-I and IGFBPs were measured by radioimmunoassays at baseline and 2 y. Mean age (63 +/- 4 y), weight (66 +/- 9 kg), and nutrient intake were correlated with the mean IGF-I concentration at baseline (172 +/- 57 microg/L) and 2 y (142 +/- 43 microg/L). IGF-I concentrations were significantly correlated with mean protein and zinc intake at baseline (r = 0.313, P = 0.001; r = 0.298, P = 0.001, respectively) and 2 y (r = 0.256, P = 0.008; r = 0.331, P = 0.001, respectively). After age, weight, and other nutrient intakes were adjusted for in multiple regression at baseline and 2 y, zinc remained the major determinant of IGF-I concentrations. These results suggest that low zinc intake is associated with low IGF-I concentrations in healthy postmenopausal women and that the effects of zinc may be independent of protein intake.
Aged↗
Diet and the prevention of osteoporotic fractures.
Explore the source record for details and available documents.
Aged↗