Influence of the vitamin D receptor gene polymorphism on bone loss in men after liver transplantation

BACKGROUND: Bone loss is a frequent complication after liver transplantation. OBJECTIVE: To investigate whether vitamin D receptor gene polymorphism influences bone loss in men after liver transplantation. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: 55 male candidates for liver transplantation. MEASUREMENTS: Lumbar spine bone mineral density was measured before and 3, 6, 12, and 24 months after liver transplantation. Vitamin D receptor genotype was determined by restriction endonuclease Bsml. RESULTS: Vitamin D receptor genotypes were significantly associated with post-transplantation changes in bone mineral density (P = 0.028). Within 3 months after transplantation, patients with the genotypes Bb or BB showed a vertebral bone loss substantially greater than that in patients with the bb genotype (between-group difference in the percentage change with respect to baseline bone mineral density, 3.7% [95% CI, 0.6% to 6.9%1). In 3 to 24 months after transplantation, bone mineral density increased steadily in the three allelic groups. CONCLUSIONS: Vitamin D receptor gene polymorphism influences bone loss after liver transplantation. Patients with the bb genotype are, to some extent, protected against post-transplantation bone loss.     

Lack of effect of intravenous pamidronate on fracture incidence and bone mineral density after orthotopic liver transplantation

BACKGROUND/AIMS: Increased rates of bone loss and fracture have been reported after liver transplantation. The aim of this study was to investigate the effects of a pre-transplant infusion of pamidronate on fracture incidence and bone loss during the first year after transplantation. METHODS: Ninety-nine adults awaiting orthotopic liver transplantation (OLT) were randomised to pamidronate or no treatment. Spinal X-rays were obtained at baseline and after 12 months. Bone mineral density (BMD) was measured at the lumbar spine (L1-4) and femoral neck at baseline, and 3, 6, and 12 months after OLT. RESULTS: The incidence of fractures in the first year after OLT was 8%, four patients within the pamidronate treated group and two in the untreated group developing fractures (P=0.40). No significant spinal bone loss occurred in either group during the first year. However, significant and sustained bone loss occurred at the femoral neck in both groups. No significant differences were seen between pamidronate treated or untreated groups at either site. CONCLUSIONS: Pamidronate in the regimen used had no significant effect on fracture rate or BMD post-transplant. The low incidence of fracture and absence of spinal bone loss indicate that bone disease after liver transplantation may be less common than previously reported.     

Bone metabolism alterations after kidney transplantation

Early after renal transplantation (RT) a rapid decrease in bone mineral density at the lumbar spine, femoral neck, and femoral shaft has been documented. In addition, an appreciable proportion of patients still remain losing bone late after RT. As a consequence, RT patients are at a high risk of bone fractures as compared to general population. Most fractures involve appendicular skeleton, particularly the feet and ankles, and the diabetic patient is at increased risk of fractures. Thus, early institution of preventive measures and treatment of established osteoporosis are central. The major cause of post-transplantation bone loss is corticosteroid treatment, and this should be used at the lower dose compatible with graft survival. Preexisting hyperparathyroidism also affects the early cancellous bone loss at the spine, and post-transplantation bone loss reflects variable individual susceptibility, resembling the polygenic determination of bone mineral density in general. Clinical trials have demonstrated that bisphosphonates or vitamin D plus calcium supplementation, prevent post-transplantation bone loss during the first 6-12 months. However, their role in preventing bone fractures has not been proven. Finally, recommendations for management, prevention and treatment, are summarized.     

Pamidronate and osteoporosis prevention in liver transplant recipients

Osteoporosis is a common complication in patients with end-stage liver disease and after orthotopic liver transplantation (LT), with resulting increasing fracture rate. In this study, we investigated the role of treatment with pamidronate in preventing further bone loss after LT. Eighty-five patients with end-stage liver disease were included in the study. Pamidronate 30 mg was given intravenously every 3 months after LT for the duration of 1 year to 43 patients with osteopenia or osteoporosis prior LT. The remainders served as controls. All patients received a supplementation of calcium and vitamin D. Bone mineral density (BMD) at the lumbar spine and the femoral neck, and markers of bone metabolism were measured before and 12 months after LT. Sixty-two BMD were available at 12 months; only paired BMD were evaluated. A significant increase in lumbar spine BMD was observed in pamidronate treated patients. No change was evident in controls. Femoral neck BMD decreased in both treated and untreated patients. Osteocalcin serum levels and deoxypyridinoline urinary excretion were significantly reduced by treatment. Our study suggests that pamidronate decreases bone turnover and is effective in preventing the course of bone loss after LT, however the efficacy, at the dosage regimen employed and in a follow-up of 12 months, appears to be limited to trabecular bone, with no effect on the cortical structure of the femur.     

Vertebral morphometry by X-ray absorptiometry before and after liver transplant: a cross-sectional study.

OBJECTIVES: To evaluate bone density and fracture prevalence in patients with end-stage liver diseases (ESLD) awaiting liver transplant and in orthotopic liver-transplant (OLTx) recipients by using dual energy X-ray absorptiometry. DESIGN: In a cross-sectional study 27 patients (16 males and 11 females, mean age 49.9 +/- 1.7 years) with ESLD, and 36 subjects (26 males and 10 females, mean age 50.5 +/- 1.6 years) who had undergone OLTx 1-70 months before, were recruited. METHODS: All patients underwent biochemical assessment of mineral metabolism. Bone density measurement of the spine and femur and morphometric X-ray absorptiometry (MXA) of the vertebrae were also obtained. RESULTS: Bone density was decreased in both groups as compared to the expected normal values. Spinal density did not differ between the two groups, while femoral bone mass was lower in OLTx than in ESLD patients (T-scores of: femoral neck -1.91 +/- 0.16 vs -1.12 +/- 0.22, P < 0.01; total femur -1.62 +/- 0.16 vs -0.94 +/- 0.23, P < 0.02). Bone alkaline phosphatase was the only independent predictor of femoral density (R2 = -0.21, P < 0.05). Symptomatic fractures were reported by 25% of OLTx and 15% of ESLD patients. MXA vertebral fractures were present in 28% of OLTx and 7.5% of ESLD (P < 0.05) patients. Most of these fractures had been asymptomatic. Total methylprednisolone intake was higher in patients with MXA vertebral fractures than in non-fractured patients (P < 0.05). CONCLUSIONS: Fragility fractures, especially of the spine, occur more frequently after liver transplantation, with corticosteroid treatment being the most important risk factor. Morphometric X-ray absorptiometry represents a useful technique for identifying vertebral fractures even in liver transplanted patients.     

Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis.

Atraumatic fractures caused by osteoporosis may be a serious complication of primary biliary cirrhosis. Mean (+/- S.D.) bone mineral density in the lumbar spine in 210 ambulatory women with primary biliary cirrhosis was 1.02 +/- 0.19 gm/cm2, 7% lower than that in 139 age-matched normal women (after adjustment for age and body weight) (p less than 0.001). Bone mineral density in the lumbar spine was inversely related to a risk score index of liver disease severity (r = -0.29, p less than 0.001). The mean rate of bone loss in 105 of these 210 women was 2%/yr +/- 4%/yr, twice as great as in the 139 normal women (p less than 0.02). In 20 women with primary biliary cirrhosis followed up after orthotopic liver transplantation, bone mineral density in the lumbar spine decreased at 3 mo (p less than 0.01), and this decrease may have resulted in atraumatic fractures in 13 of them. Bone mineral density in the lumbar spine then increased (p less than 0.01) so that by 12 mo the median bone mineral density in the lumbar spine was similar to that before transplantation and by 24 mo it was 5% above it. Therefore we conclude that the progressive bone loss observed in primary biliary cirrhosis (which is further accentuated immediately after transplantation) may be halted, and the bone mass may be restored toward normal within 2 to 3 yr after orthotopic liver transplantation.     

Fractures and avascular necrosis before and after orthotopic liver transplantation: long-term follow-up and predictive factors

With early posttransplant bone loss, orthotopic liver transplantation (OLT) recipients experience a high rate of fracturing and some avascular necrosis (AVN), but little is known about the incidence of and predictive factors for these skeletal complications. We studied 360 consecutive patients who underwent transplantation for primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and assessed both vertebral and nonvertebral (rib, pelvic, and femur) fractures in a protocolized fashion. Before OLT, 20% of the patients had experienced fracturing, and 1.4% of the patients had experienced AVN. Following OLT, there was a sharp increase in fracturing, with a 30% cumulative incidence of fractures at 1 year and 46% at 8 years after transplantation. In contrast to previous studies, there was a similar incidence of posttransplant vertebral and nonvertebral fractures. The greatest risk factors for posttransplant fracturing were pretransplant fracturing and the severity of osteopenia and posttransplant glucocorticoids. Nine percent of the liver recipients experienced AVN after OLT, and this correlated with pretransplant and posttransplant lipid metabolism, bone disease (bone mineral density and fracturing), and posttransplant glucocorticoids. A novel association between cholestasis and AVN was also identified, the mechanism for which is not known. CONCLUSION: Fortunately, recent years have seen an increase in the bone mass of liver recipients and, along with this, less fracturing and less AVN. Nonetheless, 25% of patients undergoing OLT for chronic cholestatic liver disease still develop de novo fractures after OLT; this situation demands an ongoing search for effective therapeutic agents for these patients.     

Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis

Bisphosphonates have been shown to increase bone mineral density in patients with established osteoporosis as well as those with osteopenia. The evidence conclusively shows a reduction in fracture rates in patients on the more potent nitrogen containing bisphosphonates. Indeed, significant vertebral fracture rate reduction has been demonstrated after only 1 year of therapy. Alendronate, a second-generation bisphosphonate, and risedronate, a third-generation bisphosphonate, are first line medications for the treatment of osteoporosis given their efficacy in preventing both vertebral and non-vertebral fractures. There is evidence that vertebral fractures may be prevented by intermittent cyclic therapy with etidronate. All three have been shown to increase bone mineral density in the spine, with alendronate and risedronate producing significant increases in hip bone density. Calcitonin has demonstrated the ability to reduce vertebral fracture rates with minimal changes in bone density. Calcitonin is also beneficial in reducing the bone pain associated with fractures.     

Effect of pamidronate on new vertebral fractures and bone mineral density in patients with malignant lymphoma receiving chemotherapy

BACKGROUND: High doses of corticosteroids, and the use of alkylating agents like cyclophosphamide with subsequent hypogonadism, have been implicated in the pathogenesis of chemotherapy-induced osteoporosis. In this study, we evaluated whether intravenous pamidronate can prevent bone loss and reduce vertebral fractures in patients with malignant lymphoma who were receiving chemotherapy. METHODS: We enrolled 50 patients who had newly diagnosed stage III or IV malignant lymphoma. All patients were assigned randomly to receive either intravenous pamidronate or placebo. Pamidronate (30 mg per treatment) or placebo was given at 3-month intervals for 12 months. Five patients in the control group dropped out during the trial. The main outcomes were the incidence of vertebral fractures and changes in bone mineral density of the lumbar spine and proximal femur. RESULTS: During the 12-month study, 6 (30%) of the 20 patients in the control group and 1 (4%) of the 25 patients in the pamidronate group developed new vertebral fractures (P = 0.01). In the control group, the mean percentage changes in bone mineral density were -11.2% in the lumbar spine and -4.5% in the femoral neck. In contrast, pamidronate treatment led to minor losses of bone mineral density at both sites (-2.7% at the lumbar spine; -2.3% at the femoral neck). The difference between the groups was significant at the lumbar spine (P = 0.005). CONCLUSION: Pamidronate reduces trabecular bone loss and the risk of new vertebral fractures in patients with malignant lymphoma receiving chemotherapy.     

Osteoporosis after solid organs transplantation

Osteoporosis is a common complication following kidney, heart, liver and lung transplantation. Immunosuppressive regimens to prevent graft rejection after transplantation commonly include glucocorticoids, cyclosporin A and tacrolimus which are detrimental to bone and mineral homeostasis and are superimposed on an already compromised skeleton. Additional factors likely to contribute to post-transplantation osteoporosis pathogenesis are vitamin D insufficiency, secondary hyperparathyroidism and hypogonadism. Measures should be taken to optimize bone health prior transplantation: bone mineral density and spinal X-rays should be performed, and vitamin D and gonadal status assessed. Prophylaxis against bone loss after transplantation should be considered for all patients. Data from clinical trials suggest that bisphosphonates are the most promising agents for the prevention and treatment of post-transplantation osteoporosis.     

Randomized Teriparatide [Human Parathyroid Hormone (PTH) 1-34] Once-Weekly Efficacy Research (TOWER) Trial for Examining the Reduction in New Vertebral Fractures in Subjects with Primary Osteoporosis and High Fracture Risk

Context: Weekly teriparatide injection at a dose of 56.5 μg has been shown to increase bone mineral density. Objective: A phase 3 study was conducted to determine the efficacy of once-weekly teriparatide injection for reducing the incidence of vertebral fractures in patients with osteoporosis. Design and Setting: In this randomized, multicenter, double-blind, placebo-controlled trial conducted in Japan, the incidence of morphological vertebral fractures by radiographs was assessed. Patients: Subjects were 578 Japanese patients between the ages of 65 and 95 yr who had prevalent vertebral fracture. Intervention: Subjects were randomly assigned to receive once-weekly sc injections of teriparatide (56.5 μg) or placebo for 72 wk. Main Outcome Measure: The primary endpoint was the incidence of new vertebral fracture. Results: Once-weekly injections of teriparatide reduced the risk of new vertebral fracture with a cumulative incidence of 3.1% in the teriparatide group, compared with 14.5% in the placebo group (P < 0.01), and a relative risk of 0.20 (95% confidence interval, 0.09 to 0.45). At 72 wk, teriparatide administration increased bone mineral density by 6.4, 3.0, and 2.3% at the lumbar spine, the total hip, and the femoral neck, respectively, compared with the placebo (P < 0.01). Adverse events (AE) and the dropout rates by AE were more frequently experienced in the teriparatide group, but AE were generally mild and tolerable. Conclusion: Weekly sc administration of teriparatide at a dose of 56.5 μg may provide another option of anabolic treatments in patients with osteoporosis at higher fracture risk.     

Quantitative computed tomography of the lumbar spine,not dual x-ray absorptiometry,is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy

OBJECTIVE: To determine which measurement of bone mineral density (BMD) predicts vertebral fractures in a cohort of postmenopausal women with glucocorticoid-induced osteoporosis. METHODS: We recruited 114 subjects into the study. All had osteopenia of the lumbar spine or hip, as demonstrated by dual x-ray absorptiometry (DXA), and were receiving long-term glucocorticoids and hormone replacement therapy (HRT). Measurements of BMD by DXA of the lumbar spine, hip (and subregions), and forearm (and subregions), quantitative computed tomography (QCT) of the spine and hip (n = 59), and radiographs of the thoracolumbar spine were performed on all subjects to assess prevalent vertebral fractures. Vertebral fracture prevalence, as determined by morphometry, required a >or=20% (or >or=4-mm) loss of vertebral body height. Demographic information was obtained by questionnaire. Multiple regression and classification and regression trees (CART) analyses were used to assess predictors of vertebral fracture. RESULTS: Twenty-six percent of the study subjects had prevalent fractures. BMD of the lumbar spine, total hip and hip subregions, as measured by QCT, but only the lumbar spine and total hip, as measured by DXA, were significantly associated with prevalent vertebral fractures. However, only lumbar spine BMD as measured by QCT was a significant predictor of vertebral fractures. CART analysis showed that a BMD value <0.065 gm/cm(3) was associated with a 7-fold higher risk of fracture than a BMD value >or=0.065 gm/cm(3).CONCLUSION: In postmenopausal women with osteoporosis induced by long-term glucocorticoid treatment who are also receiving HRT, BMD of the lumbar spine as measured by QCT, but not DXA, is an independent predictor of vertebral fractures.     

Bone mineral density and vertebral compression fracture rates in ankylosing spondylitis.

OBJECTIVE--To examine the relationship between disease severity and bone density as well as vertebral fracture risk in patients with ankylosing spondylitis (AS). METHODS--Measurements were taken for bone mineral density (BMD) and vertebral fracture rates in 87 patients with AS. BMD was measured at the hip (femoral neck -FN), lumbar spine (L1-L4-LS) and for the whole body using a hologic-QDR-1000/W absorptiometer. An algorithm based on normal female ranges of vertebral heights was used to define a fracture as occurring when two vertebral ratios were each three standard deviations below the calculated mean of the controls. RESULTS--Patients with AS had significantly lower FN-BMD in proportion to disease severity (based on a Schober index) and disease duration. LS-BMD was also reduced in early disease, but in patients with advanced AS it had increased considerably. Nine vertebral fractures (10.3%) were identified which was considerably higher than expected when compared with a fracture of 1.9% in a control population of 1035 females of a similar age range. Patients with AS with fractures were significantly older, more likely to be male, had longer disease duration and more advanced spinal limitation with less mobility. There was no significant reduction in lumbar spine or femoral neck bone density in the fracture group. CONCLUSIONS--Vertebral fractures that result from osteoporosis are a feature of longstanding AS. BMD used as a measure of osteoporosis of the spine in advanced AS is unreliable probably as a result of syndesmophyte formation and does not predict the risk of vertebral fracture. Alternative sites such as the neck of the femur should be used for sequential assessment of BMD in AS.     

High prevalence of osteoporotic vertebral fractures in patients with Crohn's disease

BACKGROUND AND AIMS: Osteopenia and osteoporosis are frequent in Crohn's disease. However, there are few data on related vertebral fractures. Therefore, we evaluated prospectively the prevalence of osteoporotic vertebral fractures in these patients. METHODS: A total of 293 patients were screened with dual energy x ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur. In 156 patients with lumbar osteopenia or osteoporosis (T score <-1), x ray examinations of the thoracic and lumbar spine were performed. Assessment of fractures included visual reading of x rays and quantitative morphometry of the vertebral bodies (T4-L4), analogous to the criteria of the European Vertebral Osteoporosis Study. RESULTS: In 34 (21.8%; 18 female) of 156 Crohn's disease patients with reduced bone mineral density, 63 osteoporotic vertebral fractures (50 fx. (osteoporotic fracture with visible fracture line running into the vertebral body and/or change of outer shape) and 13 fxd. (osteoporotic fracture with change of outer shape but without visible fracture line)) were found, 50 fx. in 25 (16%, 15 female) patients and 13 fxd. in nine (5.8%, three female) patients. In four patients the fractures were clinically evident and associated with severe back pain. Approximately one third of patients with fractures were younger than 30 years. Lumbar bone mineral density was significantly reduced in patients with fractures compared with those without (T score -2.50 (0.88) v -2.07 (0.66); p<0.025) but not at the hip (-2.0 (1.1) v -1.81 (0.87); p=0.38). In subgroups analyses, no significant differences were observed. CONCLUSIONS: In patients with Crohn's disease and reduced bone mineral density, the prevalence of vertebral fractures-that is, manifest osteoporosis-was strikingly high at 22%, even in those aged less than 30 years, a problem deserving further clinical attention.     

Aging bone and osteoporosis: strategies for preventing fractures in the elderly

As the older population increases, the incidence of osteoporotic fractures is expected to dramatically rise during the next few decades. Older patients are much more susceptible to fracture at any given bone mineral density (BMD) than are younger patients because of various factors, including the quality of aging bone, which involves more than BMD. Suppression of increased bone turnover by antiresorptive therapies, even with only small changes in BMD, can reduce fracture risk, especially in the lumbar spine. Bisphosphonate treatment can significantly reduce vertebral and nonvertebral fractures, including hip fractures, even in the very elderly. Prospective analyses show that risedronate therapy consistently and significantly reduces the risk of new morphometric vertebral fractures after 1 year in postmenopausal women. Post hoc analyses report significant reductions in the risk of 1 new clinical vertebral fracture after 6 months of risedronate therapy and after 1 year of alendronate therapy. Oral raloxifene therapy and salmon calcitonin nasal spray therapy have been shown to reduce the risk of vertebral fracture after 3 and 5 years, respectively, and post hoc data show a significant reduction in clinical vertebral fracture risk at 1 year with raloxifene use. However, neither raloxifene therapy nor calcitonin therapy reduce the risk of nonvertebral and hip fractures at currently approved doses. Bisphosphonates have been shown to be safe and efficacious with 7 years' risedronate sodium and 10 years' alendronate sodium data published, and bisphosphonates reduce bone turnover and increase BMD to a greater degree than raloxifene and calcitonin, which may partly account for their nonvertebral and hip fracture reduction effect. Therefore, bisphosphonate therapy with risedronate or alendronate should be considered in patients with low BMD at the hip and in older patients with osteoporosis and osteopenia, particularly those with an existing fracture.     

Regional bone mineral density after orthotopic liver transplantation

OBJECTIVES: Although there is a fall in lumbar spine bone mineral density (BMD) after liver transplantation, little is known about femoral neck or total body BMD. Therefore we determined: (a) the proportion of patients with preexisting hepatic osteopenia before transplantation and (b) the effects of transplantation on global and regional BMD. DESIGN: Retrospective analysis of BMD measurements of patients before and up to 2 years after liver transplantation. METHODS: BMD was assessed by dual energy X-ray absorptiometry in 56 patients, before and at regular intervals after liver transplantation, for up to 24 months, to measure total body, lumbar spine (L2-L4) and femoral neck BMDs. RESULTS: Pre-transplant, 23% of patients had osteoporosis (a negative Z score > 2). Paired data before and after transplantation revealed no change in total body BMD. However, there was a fall in lumbar spine BMD (1.04+/-0.03 to 1.02+/-0.03 g/cm2; P < 0.04) at 1 month after transplantation. The reduction in lumbar spine BMD was seen up to 12 months, BMD at 18-24 months being similar to pre-transplant values. Femoral neck BMD also fell (0.96+/-0.06 to 0.83+/-0.04 g/cm2; P < 0.03), but only after 6-9 months, thereafter remaining below pre-transplant values until the end of the follow-up period. CONCLUSIONS: Although osteopenia is common in patients with liver disease, total bone density does not fall after transplantation. Nonetheless regional lumbar spine and femoral neck bone density does fall after transplantation with a risk period for femoral neck fracture which may extend for up to 2 years.     

Pre-existing fractures and bone mass predict vertebral fracture incidence in women

OBJECTIVE: To determine the independent contributions of bone mass and existing fractures as predictors of the risk for new vertebral fractures. SUBJECTS: Postmenopausal Japanese-American women. MEASUREMENTS: Baseline measurements of the distal radius, the proximal radius, and the calcaneus were obtained in 1981 using single-photon absorptiometry. Measurements of the lumbar spine were obtained in 1984 using dual-photon absorptiometry. Prevalent vertebral fractures were identified using dimensions measured on lateral radiographs; vertebral height values more than 3 SD below vertebra-specific means were considered to indicate fracture. Statistical models were used to evaluate the utility of bone mass and existing (prevalent) fractures to predict the risk for new fractures during an average follow-up of 4.7 years. MAIN RESULTS: Differences of 2 SD in bone mass were associated with fourfold to sixfold increases in the risk for new vertebral fractures. A single fracture at the baseline examination increased the risk for new vertebral fractures fivefold. Presence of two or more fractures at baseline increased the risk 12-fold. A combination of low bone mass (below the 33d percentile) and the presence of two or more prevalent fractures increased the risk 75-fold, relative to women with the highest bone mass (above the 67th percentile) and no prevalent fractures. Stature, body mass index, arm span, and spinal conditions such as scoliosis, osteoarthritis, and sacroiliitis did not predict fracture incidence (P greater than 0.05). Weight was marginally predictive (P = 0.04) of fracture incidence but became nonpredictive after adjusting for bone mass (P greater than or equal to 0.05). CONCLUSIONS: Both bone mass and prevalent vertebral fractures are powerful predictors of the risk for new vertebral fractures. Combining information about bone mass and prevalent fracture appears to be better for predicting new fractures than either variable alone. Physicians can use these risk factors to identify patients at greatest risk for new fractures.     

Steroid induced osteoporosis: prevention and treatment

PURPOSE: Corticosteroid induced osteoporosis (CIO) is the most frequent complication of long-term corticosteroid therapy, and the most frequent cause of secondary osteoporosis. New data from biological, epidemiological and therapeutic studies provide basis for optimal management of this bone disease. MAIN POINTS: Corticosteroids are responsible for both quantitative and qualitative deleterious effects on bone, through their effect on bone cells, mainly on osteoblasts (with both a decrease in osteoblast activity and an increase in apoptosis). Epidemiological studies have shown an increased risk of fractures related to CIO, even for low doses, and during the first 6 months of treatment. Relative risk is 1.3 and 2.6 for peripheral and vertebral fractures respectively. Bone mineral density, measured by dual-energy X-ray absorptiometry, is decreased at spine and hip; the risk of fracture is higher in CIO as compared to post-menopausal osteoporosis, for a similar bone density. Prevention of CIO needs the use of the minimal efficacious dose, and treatment of calcium, vitamin D and gonadal hormones insufficiencies. Patients at risk of fracture, as post-menopausal women with prevalent fractures, should receive a bisphosphonate. PERSPECTIVE: It may be possible to reduce the fracture risk in patients on long-term corticosteroid therapy.     

Measurements of bone mass and bone density

X-ray-based procedures are available to measure bone mineral density in vitro at almost any skeletal site. These bone density measurements are not useful in the diagnosis of the cause of bone loss but at present are the only tests available for assessing bone mass prior to the occurrence of irreversible changes such as fractures or vertebral compression, which are easily recognizable on x-rays. When fractures are present, the severity of the bone loss and the risk for future fractures can be assessed. Repeated measurements permit estimation of the rate of bone loss, which gives useful information for monitoring treatment effect or course of the disease. Measurement of total body calcium is of less clinical importance because of the predominantly trabecular bone loss that generally occurs in metabolic bone disease. Dual-energy x-ray absorptiometry (DEXA) and quantitative computed tomography (QCT) of the spine are of about equal clinical value in the first approach to the patient with metabolic bone disease, although DEXA allows greater variety in sampling sites. For repeated measurements, DEXA provides better precision at significantly lower radiation burden. For bone mineral measurements, the lumbar spine appears to be the most sensitive skeletal site.     

36 month intermittent cyclical etidronate treatment in patients with established corticosteroid induced osteoporosis.

OBJECTIVE: To determine the longterm safety and efficacy of etidronate therapy in patients in whom corticosteroid induced bone loss has already occurred. METHODS: We performed a 36 month observational cohort study in which all data were obtained from Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients. The etidronate group consisted of 24 patients who received 400 mg of etidronate disodium for 14 days, followed by 76 days of calcium carbonate (500 mg of elemental calcium), repeated every 3 mo; the control group included 37 patients who received calcium carbonate 500 to 1000 mg daily. Outcome measurements included changes within groups from baseline and differences between groups in the bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter at 12, 24, and 36 months. The incidence of vertebral fractures was also determined. RESULTS: Etidronate therapy resulted in a meaningful percentage increase from baseline in lumbar spine BMD, primarily during the first 24 months of treatment, and this increase was sustained for the remainder of the 36 month study period (5.2%; p = 0.016). Analysis of covariance revealed a significant percentage difference (SD) between groups in lumbar spine BMD at 12 [5.5 (13.5) percent; p = 0.003] and 24 months [6.0 (17.4) percent; p = 0.011] in favor of the etidronate group. After 3 years of therapy, one patient (4%) experienced one vertebral fracture in the etidronate group, whereas 3 patients (8%) experienced 5 vertebral fractures in the control group. CONCLUSION: Etidronate treatment administered for 36 months reversed lumbar spine bone loss, and appeared to be safe in patients with established corticosteroid induced osteoporosis.