Steroid-induced Bone Loss Research Articles

Interventions for preventing bone disease in kidney transplant recipients.

People who have chronic kidney disease (CKD) have important changes to bone structure, strength, and metabolism. Children experience bone deformity, pain, and delayed or impaired growth. Adults experience limb and vertebral fractures, avascular necrosis, and pain. The fracture risk after kidney transplantation is four times that of the general population and is related to Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) occurring with end-stage kidney failure, steroid-induced bone loss, and persistent hyperparathyroidism after transplantation. Fractures may reduce quality of life and lead to being unable to work or contribute to community roles and responsibilities. Earlier versions of this review have found low certainty evidence for effects of treatment. This is an update of a review first published in 2005 and updated in 2007. This review update evaluates the benefits and harms of interventions for preventing bone disease following kidney transplantation. We searched the Cochrane Kidney and Transplant Register of Studies up to 16 May 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. RCTs and quasi-RCTs evaluating treatments for bone disease among kidney transplant recipients of any age were eligible. Two authors independently assessed trial risks of bias and extracted data. Statistical analyses were performed using random effects meta-analysis. The risk estimates were expressed as a risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous outcomes together with the corresponding 95% confidence interval (CI). The primary efficacy outcome was bone fracture. The primary safety outcome was acute graft rejection. Secondary outcomes included death (all cause and cardiovascular), myocardial infarction, stroke, musculoskeletal disorders (e.g. skeletal deformity, bone pain), graft loss, nausea, hyper- or hypocalcaemia, kidney function, serum parathyroid hormone (PTH), and bone mineral density (BMD). In this 2019 update, 65 studies (involving 3598 participants) were eligible; 45 studies contributed data to our meta-analyses (2698 participants). Treatments included bisphosphonates, vitamin D compounds, teriparatide, denosumab, cinacalcet, parathyroidectomy, and calcitonin. Median duration of follow-up was 12 months. Forty-three studies evaluated bone density or bone-related biomarkers, with more recent studies evaluating proteinuria and hyperparathyroidism. Bisphosphonate therapy was usually commenced in the perioperative transplantation period (within 3 weeks) and regardless of BMD. Risks of bias were generally high or unclear leading to lower certainty in the results. A single study reported outcomes among 60 children and adolescents. Studies were not designed to measure treatment effects on fracture, death or cardiovascular outcomes, or graft loss.Compared to placebo, bisphosphonate therapy administered over 12 months in transplant recipients may prevent fracture (RR 0.62, 95% CI 0.38 to 1.01; low certainty evidence) although the 95% CI included the possibility that bisphosphonate therapy might make little or no difference. Fracture events were principally vertebral fractures identified during routine radiographic surveillance. It was uncertain whether any other drug class decreased fracture (low or very low certainty evidence). It was uncertain whether interventions for bone disease in kidney transplantation reduce all-cause or cardiovascular death, myocardial infarction or stroke, or graft loss in very low certainty evidence. Bisphosphonate therapy may decrease acute graft rejection (RR 0.70, 95% CI 0.55 to 0.89; low certainty evidence), while it is uncertain whether any other treatment impacts graft rejection (very low certainty evidence). Bisphosphonate therapy may reduce bone pain (RR 0.20, 95% CI 0.04 to 0.93; very low certainty evidence), while it was very uncertain whether bisphosphonates prevent spinal deformity or avascular bone necrosis (very low certainty evidence). Bisphosphonates may increase to risk of hypocalcaemia (RR 5.59, 95% CI 1.00 to 31.06; low certainty evidence). It was uncertain whether vitamin D compounds had any effect on skeletal, cardiovascular, death, or transplant function outcomes (very low certainty or absence of evidence). Evidence for the benefits and harms of all other treatments was of very low certainty. Evidence for children and young adolescents was sparse. Bisphosphonate therapy may reduce fracture and bone pain after kidney transplantation, however low certainty in the evidence indicates it is possible that treatment may make little or no difference. It is uncertain whether bisphosphonate therapy or other bone treatments prevent other skeletal complications after kidney transplantation, including spinal deformity or avascular bone necrosis. The effects of bone treatment for children and adolescents after kidney transplantation are very uncertain.

The prevention and treatment of glucocorticoid-induced osteopaenia in juvenile rheumatic disease: A randomised double-blind controlled trial

BackgroundChildren and young people (CYP) with chronic rheumatic conditions; Juvenile Idiopathic Arthritis, Juvenile Systemic Lupus Erythematosus, Juvenile Dermatomyositis and Juvenile Vasculitis, treated with steroids, have low bone density, increased fracture risk and are likely to have suboptimal peak bone mass. There is currently no evidence base for the management of steroid-induced bone loss in children with rheumatic diseases. MethodsWe undertook a multi-centre double dummy double-blind randomised placebo controlled trial to investigate whether the bisphosphonate risedronate was superior to alfacalcidol or calcium and vitamin D supplementation in the prevention and treatment of steroid-induced osteopaenia in these children. Patients were stratified and randomised in a 1:1 ratio, into: placebo; alfacalcidol; risedronate. The primary outcome was the change in lumbar spine bone mineral density z score (LSaBMDz) measured by dual energy x-ray absorptiometry at one year. Secondary outcome was fracture rate. ResultsTwo hundred and seventeen patients were recruited to the study. Seventy seven placebo, 71 alfacalcidol, and 69 risedronate. Highly statistically significant differences were observed in the change in LSaBMDz between the placebo and risedronate groups; 0.274, 95% CI (0.061, 0.487) (p < 0.001) and between the risedronate and the alfacalcidol groups; 0.326 95% CI (0.109, 0.543) (p < 0.001). The difference observed between the alfacalcidol and placebo group was not statistically significant.Highly statistically significant differences were seen in the change in Total Body Less Head aBMD-Z Score between the placebo and risedronate groups (p < 0.01) but not between the alfacalcidol and risedronate groups. No significant differences in fracture frequency, adverse or serious adverse reactions were observed between the groups. ConclusionsChildren and adolescents receiving steroids for rheumatic diseases benefit from prophylactic treatment with bisphosphonates to increase LSaBMD. Alfacalcidol is ineffective.

The effects of P-gp and CYP450 modulated by rifampicin on the steroid-induced osteonecrosis of the femoral head.

This study investigated the effects of rifampicin-modulated P-glycoprotein (P-gp) and cytochrome P450 (CYP450) activity on the development of steroid-induced osteonecrosis of the femoral head. Thirty-two rabbits were equally divided into four groups: control group, oral administration group, intramuscular injection group, and local release group, in which rifampicin-loaded artificial bone graft was implanted in the left femur cavity and blank bone graft was implanted in the right femur cavity. Dexamethasone was given 1week after rifampicin administration. Peripheral P-gp activity and hepatic CYP450 content were investigated 4weeks later. Hematoxylin and eosin, Massson, and tetracycline-fluorescence staining of the femoral head were compared. In vitro, the effects of intracellular dexamethasone concentration modulated by P-gp on osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) expression and differentiation of mesenchymal stem cells were further investigated. Peripheral P-gp activity and hepatic CYP450 content in the oral administration group and the intramuscular injection group were significantly higher than those in the local release group. P-gp activity of mesenchymal stem cells in rifampicin-implanted femoral head was significantly higher than that in the blank control. Histological study showed that rifampicin could prevent steroid-induced bone loss and lipid formation, and promote new bone formation and maturation. In vitro study confirmed that intracellular dexamethasone concentration modulated by P-gp could influence the OPG/RANKL ratio and the differentiation of mesenchymal stem cells. Enhanced levels of peripheral P-gp and hepatic CYP450 can reduce the incidence of steroid-induced osteonecrosis of the femoral head. P-gp activity locally enhanced by rifampicin decreases the intracellular steroid concentration, but rifampicin does not have significant effects on peripheral P-gp and hepatic CYP450.

Bisphosphonates for steroid-induced osteoporosis.

Bisphosphonates for steroid-induced osteoporosis.

Vitamin D status of human immunodeficiency virus-positive patients with advanced liver disease enrolled in the solid organ transplantation in HIV: Multi-site study

An optimal vitamin D status may benefit liver transplantation (LT) patients. Higher levels of 25-hydroxyvitamin D [25(OH)D] mitigate steroid-induced bone loss after LT, correlate with better hepatitis C virus treatment responses, and increase graft survival. This study investigated 25(OH)D levels and assessed strategies for vitamin D deficiency prevention in human immunodeficiency virus (HIV)–positive patients with advanced liver disease who were enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study. 25(OH)D was measured in banked specimens from 154 LT candidates/recipients with the DiaSorin assay; deficiency was defined as a 25(OH)D level < 20 ng/mL. Information about vitamin D supplement use after LT was obtained from medication logs and via surveys. Logistic regression, Cox regression, and linear repeated measures analyses were performed with SAS software. We found that none of the 17 academic medical centers in the United States routinely recommended vitamin D supplements before LT, and only a minority (4/17) recommended vitamin D supplements to all patients after LT. Seventy-one percent of the 139 patients with pre-LT values had vitamin D deficiency, which was significantly associated with cirrhosis (P = 0.01) but no other variable. The vitamin D status improved modestly after LT; however, the status was deficient for 40% of the patients 1 year after LT. In a multivariate linear repeated measures model, a higher pre-LT 25(OH)D level (P < 0.001), specimen collection in the summer (P < 0.001), a routine vitamin D supplementation strategy after LT (P < 0.001), and the time elapsing since LT (P = 0.01) were significantly associated with increases in the post-LT 25(OH)D level; black race was associated with a decreased level (P = 0.02). In conclusion, the majority of patients awaiting LT were vitamin D deficient, and approximately half were vitamin D deficient after LT. More extensive use of vitamin D supplements, more sun exposure, or both are needed to prevent this deficiency in HIV-positive LT candidates and recipients. Liver Transpl 20:156-164, 2014. © 2013 AASLD.

Connexin43 Modulation of Osteoblast/Osteocyte Apoptosis: A Potential Therapeutic Target?

Connexin43 Modulation of Osteoblast/Osteocyte Apoptosis: A Potential Therapeutic Target?

A Double-Blind Placebo-Controlled Study of Intravenous Clodronate for Prevention of Steroid-Induced Bone Loss in Inflammatory Bowel Disease

Osteoporosis is common in patients with inflammatory bowel disease (IBD). Corticosteroids induce a rapid and important bone loss. Clinical trials have shown oral bisphosphonates to effectively prevent steroid-induced bone loss. However, patients with IBD have been excluded from most of these studies because of potential digestive adverse events. Clodronate is a non-amino-bisphosphonate available in intravenous form without expected digestive (as oral bisphosphonates) or proinflammatory (as amine bisphosphonates) side effects. Our aim was to assess the efficacy of intravenous clodronate in preventing steroid-induced bone loss. A 12-month, double-blind, randomized, placebo-controlled trial was conducted in IBD patients beginning a steroid therapy. Sixty-seven patients (median disease duration, 38 mo; range, 1-240 mo) were randomized to receive one infusion per 3 months of either intravenous clodronate (900 mg, n = 33) or placebo. All the patients received calcium (1 g/day) and vitamin D (800 IU/day). The main outcome was the change in lumbar bone mineral density (BMD) between baseline and 1 year. Secondary outcomes included change in femoral neck BMD and adverse events. After 1 year, there was no change in BMD in the clodronate group, neither at the spine (-0.2%, not significant) nor at the femoral neck (2.3%, NS). In contrast, there was a significant decrease in lumbar spine (-2.0%, P = .0018) and femoral neck (-1.7%, P = .045) BMD in the placebo group. Tolerance to treatment was good. Intravenous clodronate is effective in the prevention of bone loss induced by steroids in patients with IBD.

Effect of Bisphosphonates on Bone Mineral Density After Renal Transplantation as Assessed by Bone Mineral Densitometry

Introduction Steroid-induced osteoporosis is a major problem after organ transplantation. There is considerable evidence that bisphosphonates are effective in decreasing osteoporosis. Aim This prospective study was carried out to see the effects of bisphosphonates on bone mineral density (BMD) after successful renal transplantation. Material and methods Fifty consecutive patients of successful renal transplantation were randomized into two groups. Group A ( n = 27) received 35 mg/wk of Alendronate for 6 months after transplantation. Group B ( n = 23) did not receive Alendronate and served as a control. Both groups underwent a pretransplant baseline dual-energy X-ray absorptiometry (DEXA) scan of their hips and lumber spines. Both groups received oral calcium and vitamin D supplement. Both groups were matched for the regimen and dose of immunosuppressive drugs. BMD was measured at 3 months and 6 months after transplantation. Results Both groups showed a decline in BMD in early months posttransplantation. However, the 6-month DEXA scans showed a significant rise in BMD in group A as compared to group B. Conclusion Bisphosphonates appear to have a beneficial effect on steroid-induced bone loss.

Effect of risedronate on high-dose corticosteroid-induced bone loss in patients with glomerular disease

Corticosteroids are often used for the treatment of glomerular diseases. We examined whether bisphosphonate or vitamin D3 has beneficial effects on bone mineral density (BMD) in patients with glomerular diseases being treated with high-dose corticosteroids, including pulse therapy. Thirty-eight patients (19 men and 19 women, aged 42 +/- 16 years) were randomized into three groups: bisphosphonate alone (risedronate 2.5 mg/day, group R, n = 12), vitamin D3 alone (alfacalcidol 0.5 mug/day, group A, n = 15) and the combination of both agents (group R+A, n = 11). BMD at the lumbar spine was measured before and 12 months after treatment. The biochemical parameters of bone metabolism were assessed before and 3, 6 and 12 months after treatment. In group R+A, BMD was significantly increased (+2.0%), whereas BMD was significantly decreased in group A (-5.6%). The BMD in group R did not show a significant change. In patients treated with steroid-pulse, BMD was decreased in groups R and A. In group R+A, BMD was significantly increased (+2.1%). Serum osteocalcin and alkaline phosphatase levels, markers of bone formation, were significantly decreased in all groups. Urinary crosslinked N-telopeptide of type I collagen (NTx) levels, a marker of bone resorption, were decreased in groups R and R+A. In patients with decreased BMD, the urinary NTx levels at baseline were significantly higher than the patients with increased BMD. Bisphosphonate might be beneficial for the prevention of steroid-induced bone loss in patients with glomerular diseases compared with vitamin D3. The combined therapy may be more effective, especially in patients treated with high-dose corticosteroids, including pulse therapy. A high urinary NTx level before receiving corticosteroids might be a predictive marker of the loss of BMD.

Bone Densitometry in Premenopausal Women: Synthesis and Review

Abstract Bone loss prior to menopause is being increasingly identified in women. Clearly, low bone mineral density (BMD) is a significant risk factor for fracture in the estrogen-deficient female postmenopause. The significance of low bone density prior to menopause needs to be addressed. Low bone density in the premenopausal female may reflect attainment of a lower peak bone mass. It may also be secondary to progressive bone loss following achievement of peak bone density. The etiology of low bone density in the premenopausal female needs to be clarified with meticulous exclusion of secondary causes of bone loss. Menstrual status is an important determinant of peak bone mass as well as the development of bone loss in women prior to the onset of menopause. Subclinical decreases in circulating gonadal steroids may be associated with a lower peak bone mass as well as progressive bone loss in otherwise reproductively normal women. Elevations of follicle-stimulating hormone (FSH) of greater than 20 miu/L are associated with evidence of increased bone turnover marker activity and correlate with progressive bone loss in perimenopausal women. This transitional period requires further study with respect to the magnitude of bone loss experienced and the potential benefits of antiresorptive therapy. Detailed assessment of menstrual status is necessary in the evaluation of low bone density in premenopausal women. The majority of the cross-sectional and longitudinal studies completed evaluating BMD in the premenopausal years suggest that minimal bone loss does occur prior to menopause after attainment of peak bone mass. The magnitude of premenopausal bone loss, however, is controversial and may be site-dependent. More rapid rates of bone loss are seen in the transitional period beginning 2–3 yr prior to the onset of menopause. Prospective data are needed to understand further the relationship between BMD and fracture in the premenopausal period. Women with steroid-induced bone loss as well as other secondary causes of osteoporosis respond to antiresorptive therapy with documented improvements in BMD. Biomarkers can identify perimenopausal women with increased bone turnover. Lifestyle modification can improve BMD in the pre- and the perimenopausal period. Antiresorptive therapy has not been evaluated in pre- or perimenopausal women with low BMD in the absence of secondary causes of osteoporosis. As new treatment options are evaluated and become available, biomarker assessment may be of value in identifying women at risk of fracture. This paper provides a review of the literature and recommendations with respect to management of low bone density in the premenopausal female.

Resistance exercise training and alendronate reverse Glucocorticoid-Induced osteoporosis in heart transplant recipients

Background: Immunosuppression therapy with bolus glucocorticoids causes regional osteoporosis in the axial skeleton of heart transplant recipients (HTR). No preventive strategy is generally accepted for steroid-induced bone loss. Methods: To determine the efficacy of an anti-osteoporosis regimen that combined a bisphosphonate agent (alendronate sodium) with the osteogenic stimulus of mechanical loading, 25 HTRs were randomly assigned either to a group that received alendronate (10 mg/day) for 6 months (ALEN; n = 8), a group that received alendronate (10 mg/day) and performed specific resistance exercises for 6 months (ALEN + TRN; n = 8) or to a non-intervention control group (CONTR; n = 9). Alendronate was initiated at 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L-2 and L-3) was measured by dual-energy X-ray absorptiometry before and 2, 5 and 8 months after transplantation. Resistance training consisted of lumbar extension exercise (MedX) performed 1 day/week and 8 variable resistance exercises (MedX) performed 2 days/week. Results: Pre-transplantation BMD values did not differ among the 3 groups. BMD of the total body, femur neck and lumbar vertebra were significantly decreased below baseline at 2 months after transplantation in CONTR (−2.6 ± 0.9%, −5.1 ± 1.8%, −12.5 ± 4.2%, respectively), ALEN (−2.8 ± 0.8%, −5.3 ± 1.6%, −12.0 ± 3.9%) and ALEN + TRN groups (−2.7 ± 1.0%, −5.6 ± 2.1%, −11.2 ± 3.7%). CONTR had further significant losses of BMD after 3 and 6 months. ALEN had no further regional BMD losses after initiation of alendronate therapy. ALEN + TRN restored BMD of the whole body, femur neck and lumbar vertebra to within 0.9%, 2.1%, and 3.4% of pre-transplantation levels, respectively. Conclusions: Resistance exercise plus alendronate was more efficacious than alendronate alone in restoring BMD in HTRs. Our results indicate that anti-osteoporosis therapy in this population should include both an anti-resorptive agent as well as an osteogenic stimulus, such as mechanical loading.

Steroid-induced osteoporosis: how can it be avoided?

In 1932, Harvey Cushing wrote: ‘The greatly compressed bodies of the vertebrae ... were so soft they could easily be cut with a knife’. Today, steroid-induced osteoporosis is still of major clinical relevance. Glucocorticosteroids induce a biphasic bone loss with a rapid initial phase of ;10–15% during the first few months and a slower phase of ;2–5% annually. As shown in Figure 1, steroids do not only reduce the lifespan and promote the apoptosis of osteoblasts and osteoclasts but also decrease the recruitment of osteoblasts and osteoclasts from progenitor cells [1]. Apoptosis and changes in the expression of bone growth factors contribute to a decline in bone formation and the occurrence of osteonecrosis. Steroid therapy affects particularly the axial skeleton and the proximal femur. The earliest changes of steroidinduced bone loss can be detected in the lumbar spine (preferably lateral position). During long-term ()3 month) use of steroids ()7.5 mg prednisone) bone loss occurs in ;50% of patients, osteoporotic Correspondence and offprint requests to: Peter M. Jehle, MD, Klinik fur Innere Medizin, Evangelisches Krankenhaus der PaulGerhardt-Stiftung, Akademisches Lehrkrankenhaus der MartinLuther-Universitat Halle-Wittenberg, Postfach 10 02 52, D-06872 Lutherstadt Wittenberg, Germany. Email: p.jehle@pgstiftung.de Nephrol Dial Transplant (2003) 18: 861–864 DOI: 10.1093/ndt/gfg067

Fragility Fractures in Dialysis and Transplant Patients. Is it Osteoporosis, and how should it be Treated?

The term "osteoporosis" must be applied with caution to the uremic population, which has a complex range of metabolic bone disease. Trials of therapeutic interventions to prevent fractures in non uremic populations with osteoporosis cannot be generalized to uremic patients. It is unclear what, if any, role systematic bone densitometry measurement can play in the management of uremic patients who suffer "fragility" fractures--either for diagnostic purposes or to determine the effectiveness of therapy. Estrogen therapy--and perhaps SERMs (raloxifene)--appear to be a reasonable addition to conventional management of secondary HPT with calcium salts and vitamin D analogs. Using bisphosphonates to manage patients who have pre-existing fractures should be considered experimental at best. In certain circumstances, such treatment may be harmful. While the evidence is better that early therapy with intravenous pamidronate in the peri-transplant interval may mitigate the steroid-induced bone loss seen in those patients during the first 12 postoperative months, even that indication needs to be subjected to systematic clinical studies to develop appropriate clinical practice guidelines.

Glucocorticoid-induced osteoporosis.

Glucocorticoid drugs interact with bone metabolism at many levels, but their principal action is to reduce osteoblast number and bone matrix synthesis. Virtually all patients receiving glucocorticoids in doses above 5 mg per day lose bone, the amount lost being dependent on the cumulative steroid dose. The risk of fracture is also related to the individual's initial bone density, which in turn reflects race, sex, age, menopausal status, body weight, smoking and the nature of any underlying illness. Bone density measurement and personal fracture history are the best predictors of future fracture risk. Steroid-induced bone loss is reversible, so measures to minimize the systemic steroid dose or to withdraw these drugs altogether should be pursued no matter how long an individual has been using them. Increasing the calcium intake to 1.5 g per day, encouraging them to stop smoking and take more exercise, and treating any vitamin D deficiency are sensible measures in all patients. In those at high risk, bisphosphonates are the best documented interventions, although sex hormone replacement is also effective and can be used alone or in addition to bisphosphonates.

Risedronate Prevents Steroid-Induced Bone Loss

Several recent studies have shown that bisphosphonate drugs prevent bone loss associated with corticosteroid therapy (see JW Aug 15, 1998, p.130,

The treatment of steroid-induced bone loss in transplantation.

Osteopenia after transplantation is a significant cause of morbidity. Despite the lack of randomized, placebo-controlled trials in renal transplantation, there is literature supporting both the prevention and treatment of existing corticosteroid-induced osteoporosis with antiresorptive agents, such as calcitonin and bisphosphonates. The newer pharmacologic agents, nasal spray calcitonin and alendronate, have shown promising results in postmenopausal osteoporosis, and their ease of administration and low incidence of side effects make them ideal for renal transplant patients.

Not all postmenopausal women on chronic steroid and estrogen treatment are osteoporotic: predictors of bone mineral density.

Chronic steroid use results in osteoporosis, and postmenopausal women are believed to be at a high risk for steroid-induced bone loss. The purpose of this study was to determine predictors of bone mineral density (BMD) in postmenopausal women on both chronic steroid and hormone replacement therapy. Seventy-six postmenopausal women (> or = 3 years postmenopausal, > or = 2 years of steroid treatment of > or = 5 mg/day of prednisone, and > or 1 year of hormone replacement therapy) were recruited into this study. Measurements of BMD of the lumbar spine and femoral neck were obtained in all subjects. Risk factors for osteoporosis were obtained by questionnaire. Discriminant analysis was performed to determine predictors of BMD. Osteoporosis, defined by a T score of < -2.5, was present in the lumbar spine or femoral neck in 34 of the 76 subjects. Based on these criteria, women with osteoporosis were significantly older, were more years postmenopausal, and had a lower body mass index (BMI) than women who did not have osteoporosis. Predictors of osteoporosis for both the femoral neck and spine included a low BMI (P < 0.05), more years postmenopausal (P < 0.01), and more years on steroids (P < 0.01). Low BMI was the only significant predictor of osteoporosis in the lumbar spine (P < 0.05), whereas for the femoral neck both years on steroids (P < 0.05) and BMI (P < 0.05) were significant predictors of low BMD. In summary, not all postmenopausal women on chronic steroid and hormone replacement therapy are osteoporotic but a low BMI, more years on steroids, and more years postmenopausal were significant predictors of osteoporosis in these subjects.

Cyclical etidronate in the prevention of bone loss in corticosteroid-treated primary biliary cirrhosis: A prospective, controlled pilot study

Background: Recently, promising disease modifying effects of low dose corticosteroid treatment in primary biliary cirrhosis have been reported. However, steroid-induced bone loss constitutes a potential drawback of this treatment option. Aim: To assess whether etidronate can reduce bone loss during corticosteroid treatment. Methods: Twelve primary biliary cirrhosis patients (all Child-Pugh Class A), treated with prednisone in the context of a 1-year placebo-controlled pilot study with prednisone (maintenance dose 10 mg daily), and azathioprine (50 mg daily), were randomized to receive either cyclical etidronate (400 mg daily, during 2 weeks) alternated with calcium 500 mg daily during 11 weeks or calcium alone. All patients had been receving ursodeoxycholic acid during at least 1 year and this treatment was continued. Bone mass was measured in the lumbar spine and the femoral neck by dual energy X-ray absorptiometry before and after 3 and 12 months of treatment. Markers of bone formation (serum osteocalcin, procollagen-I-propeptide) and bone resorption (urinary deoxypyridinoline and calcium) were also monitored. Results: The mean lumbar bone mineral density did not significantly change in the patients taking etidronate+calcium, in contrast to patients treated with calcium alone (+0.4 vs. −3.0%; p=0.01). Changes in femoral bone mineral density and markers of bone turnover did not significantly differ between both groups. No adverse effects of etidronate were noted. Conclusions: Cyclical etidronate apppears to prevent bone loss associated with prednisone treatment in patients with primary biliary cirrhosis. These preliminary results encourage the further evaluation of long term prednisone treatment and concurrent bisphosphonate therapy in primary biliary cirrhosis.

Intranasal calcitonin keeps steroid-induced bone loss at bay

Intranasal calcitonin keeps steroid-induced bone loss at bay

Steps to prevent steroid-induced bone loss

Steps to prevent steroid-induced bone loss