Prevention of bone loss in renal transplant recipients: a prospective, randomized trial of intravenous pamidronate

Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 +/- 0.08 and 6.1 +/- 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study.     

The Effect of Alendronate on Bone Mineral Disorder in Renal Transplant Patients

PurposeIn this study, we aimed to investigate the effect of long-term administration of alendronate to treat bone loss in renal transplant patients.MethodsEighty-two renal transplant recipients were divided into 3 groups. Group 1 included patients who were treated with calcium, vitamin D3, and alendronate; group 2 included patients who were treated with calcium and vitamin D3; and group 3 included patients who did not receive these medications. All patients' sociodemographic data, biochemical parameters, and bone mineral density (BMD) measurements were recorded.ResultsThere were no significant differences between sociodemographic and laboratory findings at the beginning of study in all groups. The BMD of lumbar spine and femoral neck was significantly less in group 1 at the beginning, 12 and 24 months of the study when compared with other group. At 12 and 24 months of the study, the BMD levels were decreased both group 2 and group 3, whereas in group 1, it was stable at 12 months and increased thereafter. In group 1, the initial femoral neck BMD was negatively correlated with parathormone, sex, and body mass index, and positively correlated with creatinine level. While there was a positive correlation between basal body mass index and femur neck BMD in group 2, there was no correlation between baseline parameters, demographic data, and bone mineral density in group 3 patients.ConclusionsIn conclusion, bone loss is inevitable despite calcium and vitamin D replacement. However, bone loss can be stopped and even reversed with alendronate therapy.     

Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency

Significant reduction in bone mineral density (BMD) occurs in patients with Parkinson's disease (PD), correlating with immobilization and with vitamin D deficiency, and increasing the risk of hip fracture, especially in elderly women. As a biological indicator of compromised vitamin K status, an increased serum concentration of undercarboxylated osteocalcin (Oc) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women. We evaluated treatment with vitamin K(2) (menatetrenone; MK-4) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD. In a random and prospective study of PD patients, 60 received 45 mg of MK-4 daily for 12 months, and the remaining 60 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K(1) deficiencies, high serum levels of ionized calcium, and glutaminic residue (Glu) Oc, and low levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D], indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion. BMD in the second metacarpals increased by 0.9% in the treated group and decreased by 4.3% in the untreated group (p < 0.0001). Vitamin K(2) level increased by 259.8% in the treated group. Correspondingly, significant decreases in Glu Oc and calcium were observed in the treated group, in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures (eight at the hip and two at other sites) in the untreated group, and one hip fracture occurred among treated patients (p = 0.0082; odds ratio = 11.5). The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration, and it can also decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1,25-(OH)(2)D concentration.     

Randomized Controlled Trial of the Effects of Calcium With or Without Vitamin D on Bone Structure and Bone‐Related Chemistry in Elderly Women With Vitamin D Insufficiency

There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status. The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone‐related chemistry in elderly women with vitamin D insufficiency. Three hundred two elderly women (age, 77.2 ± 4.6 yr) with serum 25(OH)D concentrations <60 nM participated in a 1‐yr randomized, double‐blind, placebo‐controlled trial. All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol (vitamin D₂) or identical placebo (control). The effects of time and time treatment interactions were evaluated by repeated‐measures ANOVA. At baseline, calcium intake was 1100 mg/d, and 25(OH)D was 44.3 ± 12.9 nM; this increased in the vitamin D group by 34% but not the control group after 1 year (59.8 ± 13.8 versus 45.0 ± 13.3 nM, p < 0.001). Total hip and total body BMD increased significantly, and procollagen type I intact N‐terminal propeptide (PINP) decreased during the study with no difference between the treatment groups (hip BMD change: vitamin D, +0.5%; control, +0.2%; total body BMD change: vitamin D, +0.4%; control, +0.4%; PINP change: vitamin D, ?3.9%; placebo, ?2.8%). Although the fasting plasma and urine calcium increased in both groups equally, there was no detectable change in serum PTH. The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption, which fell equally in both groups (vitamin D, ?17.4%; control, ?14.8%). In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency, vitamin D₂ 1000 IU for 1 year has no extra beneficial effect on bone structure, bone formation markers, or intestinal calcium absorption over an additional 1000 mg of calcium. Vitamin D supplementation adds no extra short‐term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency.     

Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study

INTRODUCTION: Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3) have yielded conflicting results. The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D (25-OH D), bone turnover markers, bone mineral density (BMD), radius bone loss and incidence of fracture in postmenopausal women. METHODS: 669 postmenopausal women (mean age: 62.2 years) belonging to a population-based cohort were followed prospectively for a median of 11.2 years. At baseline, 25-OH D levels, BMD, bone turnover markers and clinical risk factors of osteoporosis were assessed. BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs. RESULTS: 73% and 35% of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention. 11% of women had levels below 30 nmol/l. Serum 25-OH D correlated modestly with intact PTH (r(2)=0.023, p<0.0001), but not with bone turnover markers or BMD at the hip and radius after adjustment for age. When levels of 25-OH D were considered as a continuous variable, there was no significant association between 25-OH D levels and radius BMD loss or fracture risk. After adjustment for age, there was no significant difference in incidence of fracture, BMD, radius BMD loss, bone turnover markers, grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75, 50 or 30 nmol/l. CONCLUSIONS: In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency, vitamin D status may not be an important determinant of bone health.     

Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease

A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and may have osteoporosis. We previously showed deficiency of vitamins D and K1 causes reduced bone mineral density (BMD) in female AD patients. The present study was undertaken to address the possibility that treatment with vitamin K2 (menatetrenone; MK-4) may maintain BMD and reduce the incidence of nonvertebral fractures in elderly female patients with AD. In a random and prospective study of AD patients, 100 patients received 45 mg menatetrenone, 1000 IU ergocalciferol and 600 mg calcium daily for 2 years, and the remaining 100 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K1 deficiencies. They also had high serum levels of parathyroid hormone (PTH) and Glu osteocalcin (OC) and low serum ionized calcium, indicating that vitamin D deficiency stimulates compensatory PTH secretion. During the 2-year study period, BMD in the second metacarpals increased by 2.3% in the treated group and decreased by 5.2% in the untreated group (P < 0.0001). Serum levels of vitamin K2 and 25-hydroxyvitamin D increased by 284.9% and 147.9%, respectively, in the treated group. Correspondingly, a significant decrease in Glu OC and PTH were observed, in association with an increased calcium levels, in the treated group. Twenty-two patients in the untreated group sustained nonvertebral fractures (15 with hip fractures, two fractures each at the distal forearm and the proximal femur, each one fracture at the proximal humerus, ribs, and pelvis), and three fractures (2 with hip fractures, one fracture at the proximal femur) occurred among the treated patients (P = 0.0003; odds ratio = 7.5). Treatment with MK-4 and vitamin D2 with calcium supplements increases the BMD in elderly female patients with AD and leads to the prevention of nonvertebral fractures.     

Effect of early risedronate treatment on bone mineral density and bone turnover markers after liver transplantation: a prospective single‐center study

The aim of this study was to investigate the effect of risedronate (RIS) on bone loss and bone turnover markers after liver transplantation (LT). Patients with osteopenia or osteoporosis within the first month after LT were randomized to receive RIS 35 mg/week plus calcium 1000 mg/day and vitamin D₃ 800 IU/day (n = 45) or calcium and vitamin D₃ at same dosages (n = 44). Primary endpoint was change in bone mineral density (BMD) 6 and 12 months after LT. Secondary endpoints included changes in serum β‐CrossLaps (β‐CTX) and procollagen type 1 amino‐terminal peptide (P1NP) and fracture rate. Spine X‐rays were obtained at baseline and after 12 months. There was no significant difference in BMD changes between both treatment groups at any sites; either at 6 or 12 months. Spine BMD increased in both groups at 12 months vs. baseline (P = 0.001). RIS patients had a significant increase in intertrochanteric BMD at 12 months (P < 0.05 vs. baseline). Serum β‐CTX decreased in both groups (P < 0.01), with significant differences between groups at 3 months. No significant difference in vertebral fracture incidence was found. After 12 months, BMD improved at lumbar spine and did not change at hip in both groups. Significant differences between both groups were not found. Other factors (calcium and vitamin D replacement, early prednisone withdrawal) seem to have also positive effects in BMD.     

A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs.

Vitamin D supplementation, when given with calcium, has been shown to increase bone mineral density (BMD) and reduce the incidence of hip fracture in elderly subjects. Despite its widespread use, the benefits of vitamin D supplementation in younger women and as a single agent are less clear. We performed a randomized co-twin, placebo-controlled, double-blind trial over 2 years to measure the effect of vitamin D3 supplementation on bone density and bone metabolism in young postmenopausal women. Seventy-nine monozygotic (MZ) twin pairs (mean age, 58.7 years; range, 47-70 years) were recruited. For each twin pair, one was randomized to 800 IU cholecalciferol/day for 2 years and the other was randomized to placebo. BMD was measured at the spine and hip and heel ultrasound at baseline, 12, 18, and 24 months. Samples were collected at 0, 3, and 6 months to measure serum calcium, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary deoxypyridinoline (DPD). In total, 64 pairs completed the study. No differences in baseline characteristics were seen between the groups. At 6 months, the treatment group had an increase in serum vitamin D [mean +/- SEM intrapair difference, 14.1+/-2.4 microg/liter (p < 0.001)]. There were no significant differences in other serum measurements or bone markers at 3 months or 6 months. At 24 months, no significant treatment effect was seen on BMD or calcaneal ultrasound change within pairs. Subanalysis of treatment response by vitamin D receptor (VDR) genotype revealed no significant difference in effect on BMD variables with treatment. On the basis of these results, vitamin D supplementation, on its own, cannot be recommended routinely as an osteoporosis prevention for healthy postmenopausal women with normal vitamin D levels under the age of 70 years.     

Calcium and Vitamin D Supplementation Increases Spinal BMD in Healthy, Postmenopausal Women

We undertook a double-masked, randomized, placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip, spine and forearm. The study was performed in 240 healthy women, 58–67 years of age. Duration of treatment was 2 years. Bone mineral density (BMD) was measured at the lumbar spine, hip and forearm. A dietary questionnaire was administered twice during the study and revealed a fairly good calcium and vitamin D intake (919 mg calcium/day; 3.8 mg vitamin D/day). An increase in lumbar spine BMD of 1.6% was observed in the treatment group after 2 years (p50.002). In the placebo group no significant changes were observed during the 2 years. Lumbar spine BMD was significantly higher in the treatment group at both 1 (p50.01) and 2 years (p50.05) compared with the placebo group. Though not significant, the same trend was seen at the hip. No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group. In conclusion, we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group. Together with significant changes in serum calcium and serum parathyroid hormone, this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium (calcium carbonate) and 14 mg vitamin D₃ increases intestinal calcium absorption. A positive effect on BMD was demonstrated, even in a group of early postmenopausal age, with a fairly good initial calcium and vitamin D status. Received: 2 July 1997 / Accepted: 28 October 1997     

High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer’s disease

Patients with Alzheimer’s disease (AD) are at increased risk for falls and hip fractures. To better understand causes and prevention, we measured bone mineral density (BMD) in the second metacarpals of 46 ambulatory elderly women with AD and analyzed its relation to serum biochemical indices, sunlight exposure, and vitamin D intake. BMD was significantly less than in age-matched controls. In 26% of AD patients, the serum 25-hydroxyvitamin D (25-OHD) concentration was at a deficient level (5–10 ng/mL), and in 54% it was at an osteomalacic level (<5 ng/mL). Concentrations of ionized calcium were significantly lower in patients. Conversely, concentrations of serum bone Gla-protein and urinary hydroxyproline in patients were significantly higher than in controls. BMD correlated positively with 25-OHD concentration (p = 0.0041) and negatively with parathyroid hormone (PTH) concentration (p = 0.0022). PTH was higher in patients than in controls, and correlated negatively with 25-OHD (p < 0.0001). Many AD patients were sunlight-deprived and consumed less than 100 IU of vitamin D per day. We concluded that vitamin D deficiency due to sunlight deprivation and malnutrition, together with compensatory hyperparathyroidism, contributes significantly to reduced BMD in AD patients. Low BMD increases risk of hip fractures in patients with AD, but may be improved by vitamin D supplementation.     

Recovery of Bone Mineral Density in 126 Patients after Surgery for Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT) is associated with increased fracture risk and decreased bone mass. The recovery of bone mass after surgery varies; therefore tests that predict the increase in bone mass after parathyroidectomy would be desirable. Preoperatively and at 1 year after surgery bone mineral content (BMC) in the distal radius and bone mineral density (BMD) in the lumbar spine and hip, as well as biochemical variables, were measured in 126 pHPT patients (95 women, 31 men). The mean ± SD age of the patients was 63 ± 15 years. The mean ± SD serum calcium level was 2.78 ± 0.16 mmol/L. Altogether, 60% of the patients had a low oral calcium intake, and 18% had a 25-hydroxyvitamin D₃ deficiency. Preoperatively, postmenopausal women had lower Z-scores for BMD in the hip (p < 0.001) and lumbar spine (p < 0.05) than did premenopausal women. One year after surgery the bone density had increased in about 50% of the patients. The multiple logistic regression analysis showed that there was a weak association between the change in BMD in the hip, the serum 1,25-dihydroxyvitamin D₃ level (p < 0.05), and renal function (p < 0.05), respectively. We concluded that about 50% of patients have increased bone mass after pHPT surgery, but the increase in the bone density is difficult to predict for the individual patient. Because many pHPT patients have low oral calcium intake and a vitamin D deficiency, it would be of interest to evaluate the role of postoperative calcium/vitamin D supplements.     

The Effect of Low-Dose Cholecalciferol and Calcium Treatment on Posttransplant Bone Loss in Renal Transplant Patients: A Prospective Study

Background/Aim. Posttransplant steroid doses have been reduced with the use of new and potent immunosuppressive agents. However, posttransplant osteoporosis is still a serious problem. Our aim in this study was to investigate the effect of low-dose cholecalciferol and calcium supplementation on bone loss after transplantation in renal transplant patients. Methods. Fifty-eight renal transplantation patients were included in the study. Fourteen newly transplanted patients (group 1) and 44 renal transplantation patients with a graft age of at least six months (group 2) were involved. All patients received 400 IU/day orally cholecalciferol (vitamin D3) and 600 mg/day orally calcium replacement starting from the second day posttransplantion. All patients baseline serum and urine biochemistry, serum 25-hydroxy vitamin D3 (25 (OH)D3), and bone mineral density (BMD) tests were performed. Also, the same measurements were performed at the 12th month in group 1. Results. After one year of treatment, BMDs were improved in group 1. Patients in group 1 had a nonsignificant increase of lumbar spine (8.12 ± 18.64% of baseline BMD) and femoral total (7.10 ± 13.48% of baseline BMD) BMD at the end of the first year. On the other hand, there was a significant increase in femoral neck (10.06 ± 15.70% of baseline BMD, p < 0.05) measurements. The baseline results of group 2 were similar to group 1. In group 1, 25 (OH)D3 levels were increased while PTH levels were decreased at the end of the year. Conclusion. In renal transplant patients who use low-dose metilprednisolon and new immunosuppressive agents together, low doses of vitamin D3 and calcium replacement for one year provides a reduction in lumbar spine, femoral neck, and femoral total bone loss and prevents bone loss in group 2. In addition, it contributed to the normalization of PTH levels.     

Characteristics of lifetime factors,bone metabolism,and bone mineral density in patients with hip fracture

Seventy-four postmenopausal women with nonpathological hip fracture were recruited to a study in which they were compared for lifetime factors, some biochemical measurements of bone metabolism, and bone mineral density (BMD), with 40 age-adjusted controls without fracture. The fracture patients were less independent; their walking ability was weaker; their vision was poorer; they had more general diseases (strokes, diabetes, malignant diseases, heart and vascular diseases); more of them had had deliveries; and they were using significantly more loop diuretics, and antidepressant, neuroleptic, and diabetes drugs than the controls. Thirty-seven patients and 19 controls were excluded from the statistical comparison of BMD and the biochemical measurements of bone metabolism because they had had treatments with calcium, vitamin D, bisphosphonates, estrogens, calcitonin, or corticosteroids, and one fracture patient was excluded for primary hyperparathyroidism. The BMD of the upper femur was significantly lower in the fracture group compared with the control group. Serum total calcium (S-Ca) and serum vitamin D (S-25-(OH)-D) were significantly lower and the levels of calcitonin (S-CT) significantly higher in the fracture group than in the control group, but none of the bone formation markers showed significant differences between the study groups. A comparison of patients with cervical and trochanteric fractures showed BMD to be significantly lower in the upper femur in the trochanteric fracture group. There were no significant differences in the biochemical measurements (with the exception that S-CT was higher in the cervical fracture group), nor in the lifetime factors between the fracture types. In conclusion, some lifetime factors and low S-Ca, low S-25-(OH)-D, high S-CT, and low BMD of the upper femur seem to be related to the risk of hip fracture, and low BMD and low S-CT seem to be related to the trochanteric fracture type in postmenopausal women.     

Bone Mineral Density in Females after Jejunoileal Bypass: A 25-year Follow-up Study

Background: Jejunoileal (JI) bypass was a widely performed operation for morbid obesity in the 1970s.The aim of this study was to investigate the long-term status of bone mineral density (BMD) after weight loss induced by this technique. Subjects and Methods: 18 female patients (age 48-79 y, BMI 23-43 kg/m2) had BMD measurements performed 25 years after JI bypass. Dual energy x-ray absorptiometry was used, and measured sites were the lumbar spine L2-L4, left femoral neck and total hip. Vitamin and mineral supplementation had not routinely been prescribed. An assessment was made on age-adjusted BMD values, and as to whether present BMD was related to present demographic and biochemical variables. Results: No significant reduction of BMD was found beyond that which was expected for age. BMD was inversely and separately related to age and body weight. The serum level of vitamin D was low in 45% of the patients, and inversely correlated to body weight and BMI. Alk phosphatase and parathyroid hormone were the best markers for low BMD. Conclusion: These results suggest that JI bypass has not been detrimental to bone density in females. We recommend, however, vitamin D and calcium supplements after malabsorptive procedures for morbid obesity.     

Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study.

Few studies have evaluated risk factors for bone loss in elderly women and men. Thus, we examined risk factors for 4-year longitudinal change in bone mineral density (BMD) at the hip, radius, and spine in elders. Eight hundred elderly women and men from the population-based Framingham Osteoporosis Study had BMD assessed in 1988-1989 and again in 1992-1993. BMD was measured at femoral neck, trochanter, Ward's area, radial shaft, ultradistal radius, and lumbar spine using Lunar densitometers. We examined the relation of the following factors at baseline to percent BMD loss: age, weight, change in weight, height, smoking, caffeine, alcohol use, physical activity, serum 25-OH vitamin D, calcium intake, and current estrogen replacement in women. Multivariate regression analyses were conducted with simultaneous adjustment for all variables. Mean age at baseline was 74 years +/-4.5 years (range, 67-90 years). Average 4-year BMD loss for women (range, 3.4-4.8%) was greater than the loss for men (range, 0.2-3.6%) at all sites; however, BMD fell with age in both elderly women and elderly men. For women, lower baseline weight, weight loss in interim, and greater alcohol use were associated with BMD loss. Women who gained weight during the interim gained BMD or had little change in BMD. For women, current estrogen users had less bone loss than nonusers; at the femoral neck, nonusers lost up to 2.7% more BMD. For men, lower baseline weight and weight loss also were associated with BMD loss. Men who smoked cigarettes at baseline lost more BMD at the trochanter site. Surprisingly, bone loss was not affected by caffeine, physical activity, serum 25-OH vitamin D, or calcium intake. Risk factors consistently associated with bone loss in elders include female sex, thinness, and weight loss, while weight gain appears to protect against bone loss for both men and women. This population-based study suggests that current estrogen use may help to maintain bone in women, whereas current smoking was associated with bone loss in men. Even in the elderly years, potentially modifiable risk factors, such as weight, estrogen use, and cigarette smoking are important components of bone health.     

Six-year follow-up study of bone mineral density in patients with systemic lupus erythematosus

Summary

Long-term bone mineral density (BMD) changes and the associated factors in systemic lupus erythematosus (SLE) patients were assessed. Despite the remarkably low overall bone loss, significant spine bone loss was associated with the use of glucocorticoids, use of antimalarials, and lower 25-hydroxyvitamin D levels, stressing the importance of prevention of osteoporosis and vitamin D deficiency in SLE patients.

Introduction

The aim of this study is to assess the BMD changes in patients with SLE and to identify the associated factors.

Methods

Demographic and clinical data of 126 SLE patients were collected, and BMD measurements of the lumbar spine and the total hip were performed by dual-energy X-ray absorptiometry at baseline and follow-up. Statistical analyses were performed using independent Mann–Whitney U tests and linear regression analyses.

Results

At baseline, 39.7 % of the patients (90 % female, mean age 39?±?12.2 years) had osteopenia, and 6.3 % had osteoporosis. The median follow-up duration was 6.7 years (range 1.9–9.3 years). Mean changes in BMD at the lumbar spine (?0.08 %/year) and the hip (?0.20 %/year) were not significant. During follow-up, 70 % of the patients used glucocorticoids. The mean ± SD daily glucocorticoid dose was 5.0?±?5.0 mg. In multiple regression analysis, BMD loss at the spine was significantly associated with higher daily glucocorticoid dose and lower baseline 25-hydroxyvitamin D levels. BMD loss at the hip was associated with lower 25-hydroxyvitamin D levels at baseline, reduction of body mass index, and baseline use of antimalarials.

Conclusions

In this 6-year follow-up study, bone loss was remarkably low. A dose-dependent relationship between glucocorticoid use and spinal bone loss was found. In addition, the use of antimalarials and lower 25-hydroxyvitamin D levels at baseline were associated with BMD loss. These findings underline the importance of prevention and treatment of vitamin D deficiency and osteoporosis in SLE, especially in patients using glucocorticoids or antimalarials.     

Vitamin D insufficiency does not affect response of bone mineral density to alendronate

Summary  We investigated whether osteoporosis therapy with alendronate in postmenopausal patients is equally effective in patients who are vitamin D insufficient as in those who are vitamin D sufficient. We found that vitamin D insufficiency is common among patients with low bone density but that vitamin D insufficiency did not impair response to alendronate. Introduction  Treatment of vitamin D deficiency leads to significant improvements in bone mineral density (BMD); however, whether insufficiency affects BMD’s response to bisphosphonate therapy is unknown. Methods  To determine whether vitamin D insufficiency at initiation of alendronate therapy for low BMD affects treatment efficacy, we used data from 1,000 postmenopausal women randomly selected from the vertebral fracture arm (n = 2,027) of the placebo-controlled Fracture Intervention Trial of alendronate. Participants were randomly assigned to placebo (50%) or alendronate therapy and most (83%) to calcium (500 mg/day) and cholecalciferol (250 IU/day). We measured serum 25-hydroxy vitamin D (25OHD) at enrollment, then categorized baseline vitamin D status according to 25OHD concentration ( ≤ 10 ng/ml = deficient; >10 but ≤ 30 ng/ml = insufficient; >30 ng/ml = sufficient) and used linear regression to compare the effects of alendronate treatment among these categories. Results and conclusion  At baseline, participants were vitamin D sufficient (14%), insufficient (83%), and deficient (2%). We found that BMD response to therapy at total hip or spine did not vary by vitamin D status at baseline (p for heterogeneity = 0.6). We determined that vitamin D insufficiency is common among participants with low BMD. However, vitamin D status at initiation of therapy does not affect BMD’s response to alendronate, when it is coadministered with cholecalciferol and calcium. Scholar’s Grant from the National Osteoporosis Foundation (to D.M.A) and National Institutes of Health grant K23 RR020343 (to D.M.A).     

Randomised double blind placebo controlled trial investigating the effect of calcium and vitamin D supplementation on bone mineral density and bone metabolism in adult patients with cystic fibrosis

BACKGROUND: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis and might be related to calcium and vitamin D malabsorption from the gastrointestinal tract. The aim of this study was to investigate the effect of calcium and vitamin D supplementation on BMD and bone metabolism in these subjects. METHODS: Patients were invited to participate if they had a BMD Z score of -1 or less in the lumbar spine, proximal femur or distal forearm. Patients were randomised to receive calcium 1 g+vitamin D 800 IU or placebo daily, in addition to their regular vitamin D supplements (900 IU/day). BMD and bone biochemical markers were measured before and after 1 year of treatment. RESULTS: After 12 months, the treatment group (n=15) showed a reduced rate of bone loss compared with the control group (n=15) in the lumbar spine (mean difference 1.9% [CI -0.9% to 4.6%]), total hip (mean difference 0.7% [CI -2.2% to 3.5%]) and distal forearm (mean difference 1.7% [CI -2.2% to 5.5%]), but these changes did not reach statistical significance. There was also a trend towards a reduction in bone turnover in the treatment group. CONCLUSIONS: Calcium and vitamin D supplementation reduced the rate of bone turnover and bone loss in adult patients with cystic fibrosis, but these changes did not reach statistical significance. These data suggest that a longer term trial of this simple intervention would be justified.     

Bone mineral density 6 years after a hip fracture: a prospective, longitudinal study

The purpose of this prospective study was to extend the results of previous studies to determine if an accelerated rate of loss of bone mineral density (BMD) continues for 6 years after a hip fracture. Eighty-five elderly patients who had sustained a hip fracture had determinations of BMD made at the time of fracture; 55 of these patients were available for reassessment of BMD 1 year later, and 21 were available for reassessment of BMD 6 to 7 years later. The change in BMD from injury to 1 year and from 1 to 6 years was determined and correlated with pre- and postinjury variables, such as ambulatory ability, dietary intake of calcium, serum vitamin D levels, and mental status. There was a marked decrease in BMD in the in the first year after fracture, with the mean change in BMD being -4.3% at the femoral neck and -1.8% at the lumbar spine. Between 1 and 6 years after fracture, however, there was a dramatic increase in the BMD at both the femoral neck and lumbar spine measurement sites. Relative to 1 year after fracture, the mean increases were 7.7% at the femoral neck and 4.5% at the lumbar spine. In many cases, the loss of bone mineral that occurred in the first year after fracture was completely recouped in the subsequent 5 years. Five of the 21 patients (24%) sustained a contralateral hip fracture in the 6 years after the index fracture. Lumbar spine BMD was lower at baseline (p = 0.112), 1 year after fracture (p = 0.007), and 6 years after fracture (p = 0.003) in patients who sustained a second hip fracture than in those who did not. There was a general decrease in the functional activity level of patients in the 6 years after a hip fracture, but there were no statistically significant relationships between changes in BMD and the functional mobility of patients. The mean calcium intake in patients improved remarkably in the 6 years after fracture, but there was no correlation between daily calcium intake and changes in BMD. During the first year after a hip fracture, there is a rapid loss of bone mineral from the lumbar spine and contralateral femoral neck. Between 1 and 6 years after fracture, however, BMD is likely to increase, perhaps to levels greater than those at baseline. Although this investigation is small, the findings of this study point to the importance of further larger studies to further clarify the natural history of BMD after a hip fracture and the potential impact of pharmacological intervention on that natural history.