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.     

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long-term follow-up of a prospective study

Reduced bone mineral density (BMD) has been reported following allogeneic stem cell transplantation (alloSCT) but the effects of autologous SCT (autoSCT) are less well characterized. We performed a prospective study of BMD changes and its determinants in 44 SCT recipients (38 auto and six allo; 30 peripheral blood SCT and 14 bone marrow transplantation). Serial measurements of BMD at the lumbar spine and femoral neck were performed at baseline and at 3, 6, 12 and 24 months, and spinal radiographs were performed at baseline and 12 months. Mean baseline BMD values at the femoral neck and spine were within normal limits. At 3 months, there was a significant decline of BMD at the femoral neck (P = 0.011) and a non-significant trend towards reduction at the spine. BMD loss persisted for up to 2 years at the femoral neck (P = 0.005), but values returned to baseline at the spine. Reflecting the rapid initial decline in BMD, bone-specific alkaline phosphatase (a serum marker of bone formation) showed a significant initial decline at 1 month but had recovered to pretransplant levels by 3 months. No new fractures were detected at 1 year post transplant. Sex, diagnosis, use of total body irradiation, stem cell source and type of graft (auto versus allo) did not significantly predict BMD change over the first 12 months. In conclusion, significant and persistent bone loss at the femoral neck was demonstrated in this group of patients following stem cell transplantation. The implications of these findings for future fracture risk require further study.     

Pamidronate reduces bone loss after allogeneic stem cell transplantation

BACKGROUND: Rapid bone loss occurs from the proximal femur after allogeneic stem cell transplantation (alloSCT). Objective: The objective of the study was to evaluate effects of high-dose pamidronate therapy on bone loss (BMD) after alloSCT. DESIGN: This was a randomized, multicenter, open-label, 12-month prospective study of iv pamidronate (90 mg/month) beginning before conditioning vs. no pamidronate. All 116 patients also received calcitriol (0.25 microg/d) and calcium (1000 mg/d), which were continued for another year. MAIN OUTCOME MEASURES: Primary objectives were to compare changes in BMD 12 months after alloSCT at the femoral neck, lumbar spine, and total hip between the treatment arms and assess influences of glucocorticoid and cyclosporin therapy on these changes. RESULTS: Pamidronate reduced bone loss at the spine, femoral neck, and total hip by 5.6, 7.7, and 4.9% (all P < or = 0.003), respectively, at 12 months. However, BMD of the femoral neck and total hip was still 2.8 and 3.5% lower than baseline, respectively (P < 0.05) with pamidronate. Only differences at the total hip remained significant between the two groups at 24 months. Benefits were restricted to patients receiving an average daily prednisolone dose greater than 10 mg and cyclosporin therapy for more than 5 months within the first 6 months of alloSCT. CONCLUSIONS: Pamidronate markedly reduced but did not completely prevent postallogeneic bone marrow transplantation bone loss. BMD benefits were greatest in patients on higher doses of immunosuppressive therapy, but most were lost 12 months after stopping pamidronate. Studies of more potent bisphosphonates or anabolic therapy with PTH after alloSCT are warranted with the aim of durable maintenance of bone mass.     

Incidence of vertebral fractures in the first three months after orthotopic liver transplantation

BACKGROUND AND OBJECTIVES: High rates of bone loss and increased fracture incidence have been reported in patients undergoing liver transplantation, mainly within the first post-operative year. The pathogenesis of post-transplantation bone disease has not been clearly established, but the high doses of glucocorticoids used for immunosuppression may contribute. The use of lower doses in recent years has been associated, in some studies, with lower rates of bone loss and decreased fracture incidence. The aim of this prospective study was to establish the incidence of vertebral fractures in the first 3 months in patients undergoing liver transplantation for chronic liver disease and to identify risk factors for fracture in these patients. DESIGN AND METHODS: Thirty-seven adults with end-stage liver disease were studied prospectively prior to and 3 months after liver transplantation. Vertebral fractures were assessed semi-quantitatively from lateral spine X-rays and bone mineral density measured using dual energy X-ray absorptiometry. RESULTS: Prior to transplantation, prevalent vertebral fractures were present in 13 patients (35%). New fractures developed after transplantation in 10 patients (27% of total) and were significantly more common in those with a prevalent vertebral fracture pre-operatively (P<0.02). Osteoporosis, defined as a bone mineral density T score below -2.5, was present in 39% of patients prior to transplantation, but bone mineral density was not helpful in predicting incident fracture, whether measured before or after transplantation. Over the 3-month study period, significant bone loss occurred in the femoral neck (P<0.05) but not the lumbar spine. CONCLUSIONS: Our results demonstrate a high incidence of vertebral fracture in the first 3 months after liver transplantation and indicate that prevalent vertebral fracture is an important risk factor for the subsequent development of fracture in these patients. Prevention of post-transplantation bone disease should focus both on optimizing bone mass prior to transplantation and preventing bone loss in the early post-operative period.     

Predicting bone loss following orthotopic liver transplantation

BACKGROUND: Hepatic osteodystrophy occurs in the majority of patients with advanced chronic liver disease with the abnormalities in bone metabolism accelerating following orthotopic liver transplantation (OLT). AIMS: To examine changes in bone mineral density (BMD) following OLT and to investigate factors that lead to bone loss. METHODS: Twelve patients had BMD (at both the lumbar spine (LS) and femoral neck (FN)) and biochemical markers measured preoperatively and for 24 months following OLT. RESULTS: BMD was low in 75% of patients prior to OLT and decreased significantly from baseline at the LS at three months and the FN at six months. BMD began to increase thereafter at both sites, approaching baseline values at the LS by 12 months. Bone formation markers, osteocalcin and procollagen type I carboxy propeptide, decreased immediately post-OLT, with a concomitant increase seen in the resorption markers pyridinoline and deoxypyridinoline. This resulted in a negative uncoupling index early post-OLT, that rebounded to positive values after six months. There was a significant correlation between the change in the uncoupling index between six and three months which preceded the increase in BMD at 12 months. The decrease in BMD recorded early post-OLT correlated with vitamin D levels at three months. CONCLUSIONS: Results suggest that increased resorption and inadequate formation are the major contributors to additional bone loss following OLT. Non-invasive biochemical markers precede later changes in BMD in this patient group following OLT and may have a role in investigating and planning intervention strategies to prevent bone loss in future studies.     

Relationship between bone mineral density changes and fracture risk reduction in patients treated with strontium ranelate

OBJECTIVE: Our objective was to analyze the relationship between bone mineral density (BMD) changes and fracture incidence during 3-yr treatment with strontium ranelate. PATIENTS: Women from the strontium ranelate arm of the Spinal Osteoporosis Therapeutic Intervention study and the TReatment Of Peripheral OSteoporosis study were evaluated. OUTCOME MEASURES: The outcome measures included BMD at the lumbar spine, femoral neck, and total proximal femur assessed at baseline and after a follow-up of 1 and 3 yr; semiquantitative visual assessment of vertebral fractures; and nonvertebral fractures based on written documentation. RESULTS: After 3 yr of strontium ranelate treatment, each percentage point increase in femoral neck and total proximal femur BMD was associated with a 3% (95% adjusted confidence interval, 1-5%) and 2% (1-4%) reduction in risk of a new vertebral fracture, respectively. The 3-yr changes in femoral neck and total proximal femur BMD explained 76% and 74%, respectively, of the reduction in vertebral fractures observed during the treatment. Three-year changes in spine BMD were not statistically associated with the incidence of new vertebral fracture (P = 0.10). No significant associations were found between 3-yr changes in BMD and incidence of new nonvertebral fractures, but a trend was found for femoral neck BMD (P = 0.09) and for total proximal femur BMD (P = 0.07). An increase in femoral neck BMD after 1 yr was significantly associated with the reduction in incidence of new vertebral fractures observed after 3 yr (P = 0.04). CONCLUSION: During 3-yr strontium ranelate treatment, an increase in femoral neck BMD was associated with a proportional reduction in vertebral fracture incidence.     

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.     

Prevention of bone loss after allogeneic stem cell transplantation by calcium, vitamin D, and sex hormone replacement with or without pamidronate

CONTEXT: In controlled studies, bisphosphonates have been used to prevent bone loss after solid organ transplantations but not in conjunction with stem cell transplantation (SCT). OBJECTIVE: The objective of the study was to test whether additional iv pamidronate would prevent bone loss associated with SCT more effectively than the combination of calcium, vitamin D, and sex steroid replacement therapy alone. SETTING: The study was carried out at the Helsinki University Central Hospital. PATIENTS, DESIGN, INTERVENTION: Ninety-nine adult recipients of allogeneic SCT were randomized by age and gender into two groups. In one group, the patients received 1000 mg calcium carbonate and 800 IU vitamin D daily, and females received estrogen and males received testosterone replacement therapy. In another group, the patients received the same treatments plus six iv infusions of 60 mg pamidronate before and 1, 2, 3, 6, and 9 months after SCT. MAIN OUTCOME MEASURES: Bone mineral density (BMD) of the lumbar spine and the upper femur, measured by dual-energy x-ray absorptiometry, and bone turnover markers were followed for 12 months. RESULTS: In the pamidronate group, lumbar spine BMD remained stable but decreased in the other group by 2.9% at 12 months (P = 0.0084 between the groups over time). Total hip BMD reduced 5.1% in the pamidronate group and 7.8% in the other group by 12 months (P = 0.0015), and femoral neck BMD reduced 4.2 and 6.2%, respectively (P = 0.074). In the pamidronate group, serum type I procollagen amino-terminal propeptide (P = 0.032 between the groups over time) and urinary type I collagen amino-terminal telopeptide (P = 0.035) decreased 79 and 68% during the first 3 months, and remained lowered thereafter, but did not change in the other group. CONCLUSIONS: The recipients of allogeneic SCT receiving additional pamidronate sustain less bone loss than those treated with calcium, vitamin D, and sex steroid replacement alone. Despite all the efforts, however, bone loss is not totally abolished at the hip.     

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.     

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.     

Bone loss following hematopoietic stem cell transplantation: a long-term follow-up

Transplantation-associated bone loss is a well-known phenomenon, however, effects of hematopoietic stem cell transplantation are insufficiently characterized. We conducted a prospective, unicentric, long-term follow-up in 280 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Bone mineral density (BMD) was measured before transplantation and then yearly for at least 4 years. Patients received vitamin D plus calcium until steroid withdrawal. Mean baseline BMD was normal. We demonstrated significant bone loss with nadir BMD at month 6 for the spine and at month 24 for total body and femoral neck. Average annual bone loss was 0.6% for spine, 0.4% for total body, 2.3% for femoral neck, and 3.5% for Ward triangle. While spine and total body BMD returned to baseline, bone loss at femoral neck sites was attenuated, but BMD did not return to baseline until month 48 (P <.0001 for femoral neck and Ward triangle). Univariate factor analysis of 15 potential risk factors for rapid bone loss revealed a positive correlation of bone loss with steroid and cyclosporine A use, baseline BMD, and loss of muscle mass (overwhelming power of steroid use in multifactor analysis). Such rapid BMD changes probably increase fracture risk consecutive to irreversible microarchitectural changes even if osteodensitometry shows long-term recovery.     

Comparison of PA spine, lateral spine, and femoral BMD measurements to determine bone loss in ankylosing spondylitis

To evaluate bone loss in the early- and late-stage ankylosing spondylitis (AS) patients using posteroanterior (PA) and lateral lumbar and femoral bone mineral density (BMD) measurement methods. Eighty-six AS patients and 50 control subjects were enrolled. PA spine, lateral spine, and femur BMD values of patients and controls were measured. The presence of any syndesmophytes or compression fractures was determined. Patients were divided as early (<10 years) and late stage (≥10 years) according to the onset of the inflammatory pain. Mean PA spinal BMD was similar in patients and controls (p = 0.460). Femoral and lateral spine BMD values were significantly lower in patients (p = 0.012 and p = 0.001). When comparing early- and late-stage AS groups, mean PA spinal BMD was found to be lower in the early group (p = 0.005), while femoral and lateral spinal values were lower (although statistically not significant) in the late group. At least one compression fracture was present in 28 % of patients. Although not statistically significant, mean PA spinal BMD was higher in those with fractures. Femoral and lateral spinal BMD values were significantly lower in the fracture group (p = 0.034 and p = 0.004). Lateral spinal BMD values were significantly lower in patients with syndesmophytes (p = 0.004). Bone loss is increased in AS compared with control subjects. The BMD measurement at the lateral lumbar spine reflects bone loss and fracture risk better than PA spine and femoral measurements.     

The effect of nandrolone decanoate on bone mineral density, muscle mass, and hemoglobin levels in elderly women with osteoporosis: a double-blind, randomized, placebo-controlled clinical trial

METHODS: In a randomized, double-blind, placebo-controlled clinical trial, we evaluated the effect of a 2-year treatment with nandrolone decanoate (ND) on bone mineral density (BMD) of lumbar spine, femoral neck, and trochanter and on vertebral fracture rate, muscle mass, and hemoglobin levels. Sixty-five osteoporotic women older than 70 years were studied. Thirty-two patients received injections of 50 mg ND, and 33 received placebos every 3 weeks. All patients received 500 mg calcium tablets daily. RESULTS: Compared to baseline, ND increased the BMD of the lumbar spine (3.4% +/- 6.0 and 3.7% +/- 7.4; p < .05) and femoral neck (4.1% +/- 7.3 and 4.7% +/- 8.0; p < .05) after 1 and 2 years, respectively. The BMD of trochanter increased significantly only after the first year (4.8% +/- 9.3, p < .05). Compared to the placebo group, the ND group presented with significantly increased BMD of the trochanter and neck. ND significantly reduced incidence of new vertebral fractures (21% vs 43% in the placebo group; p < .05). ND showed a significant statistical increase in lean body mass after the first (6.2% +/- 5.8; p < .01) and second years (11.9% +/- 29.2; p < .01). In addition, a 2-year treatment with ND significantly increased hemoglobin levels compared to baseline (14.3%; p < .01) and placebo (p < .01). CONCLUSIONS: ND increased BMD, hemoglobin levels, and muscle mass, and reduced the vertebral fracture rate of elderly osteoporotic women.     

Vertebral fracture risk reduction with risedronate in post-menopausal women with osteoporosis: a meta-analysis of individual patient data

BACKGROUND AND AIMS: The effect of risedronate, a potent pyridinyl bisphosphonate, on vertebral fractures in post-menopausal women was evaluated in randomized, placebo-controlled clinical trials. These trials included two large vertebral fracture studies that used time-to-event methods to evaluate the effects of treatment on fracture risk, thereby allowing both the occurrence and the timing of fractures to be considered. METHODS: We used individual patient data (IPD) and time-to-event methods to perform a meta-analysis of the anti-fracture efficacy of risedronate (2.5 or 5 mg daily) in osteoporotic women enrolled in five double-blind, placebo-controlled clinical trials. Women were included in the analysis if, at baseline, they had either at least one prevalent vertebral fracture or a femoral neck bone mineral density (BMD) T-score of less than -2.5, were at least 1 year post-menopausal, and had had vertebral fracture assessments (N = 3331). RESULTS: Risedronate 5 mg daily reduced the risk of radiographically defined vertebral fracture by 64% (95% CI, 46 to 76%, p < 0.001) in the first year of treatment and 45% (95% CI, 31 to 57%, p < 0.001) in 3 years. The numbers of patients who needed to be treated with risedronate 5 mg to prevent one new vertebral fracture over 1 and 3 years were 21 and 13, respectively. Comparable findings were observed in sub-populations defined on the basis of either prevalent vertebral fracture without regard to femoral neck BMD, or femoral neck BMD without regard to vertebral fracture status. Risedronate significantly reduced the incidence of clinical (symptomatic) vertebral fractures in the first 6 months of treatment (p < 0.001). CONCLUSIONS: This meta-analysis, based upon five trials and using IPD and time-to-event statistical methods, provides a more precise estimate of the effect of risedronate in reducing vertebral fracture risk in postmenopausal osteoporotic women than a meta-analysis using summary statistics from the literature.     

Fracture thresholds in osteoporosis: implications for hormone replacement treatment.

The bone mineral densities of the lumbar spine and femoral neck were determined by dual energy chi ray absorptiometry in 110 women aged 40-82 years (average 65 years) with spinal osteoporosis who had had at least one atraumatic vertebral compression fracture and in 1026 normal women aged 40-79 years (average 52 years). The women with osteoporosis showed a significant decrease in bone mineral density (BMD) at the lumbar spine and femoral neck compared with age matched normal women (sixth decade of life -26% spine, -23% femoral neck; seventh decade -26% spine, -16% femoral neck). The fracture threshold, defined as the 90th centile of spinal BMD for women with osteoporosis, was 0.81 g/cm2 at the lumbar spine and 0.656 g/cm2 at the femoral neck. Five per cent of normal women aged 40-49 years, 20% aged 50-59 years, and 45% aged 60-69 years had a BMD below this threshold. To maintain the bones of women above the fracture threshold until the age of 70 years about 50% of postmenopausal women need hormone replacement therapy. However, if the BMD is to be kept above the fracture threshold for a women's lifetime, e.g. until the age of 80-90 years, then most women will need treatment, though for various lengths of time depending on their initial BMD. Measurements of BMD in postmenopausal women currently help in identifying the risk of osteoporotic fractures but in the lifetime assessment of risk in a single subject they may have a more important role in deciding the duration of hormone replacement therapy.     

Secondary osteoporosis in liver transplant recipients: a longitudinal study in patients with and without cholestatic liver disease

BACKGROUND: Metabolic bone disease is one of the major long-term complications in liver transplant recipients, but it remains unclear which patients are at highest risk for developing severe bone disease following transplantation. METHODS: A total of 46 consecutive, adult patients with chronic liver disease accepted for a liver transplantation waiting list were prospectively included in the study. The patients were classified into two groups: group A--chronic cholestatic liver disease (n = 28), and group B--chronic non-cholestatic liver disease (n = 18). Bone mineral density (BMD) was measured at acceptance for the waiting list and at 3, 12 and 36 months following transplantation. Markers of bone turnover (serum-bone specific alkaline phosphatases (bALP), s-osteocalcin, s-1-collagen-C-terminal telopeptide (1-CTP) and urine N-terminal telopeptides u-Ntx) were measured at acceptance and at 3, 6, 12, 24 and 36 months following transplantation. BMD and markers of bone turnover were compared with similar values in a matched control group of 42 healthy individuals. RESULTS: BMD decreased significantly during the early post-transplantation period (median bone loss femoral neck (FN) 3 months post-transplant 8.5%). BMD levels declined slightly from 3 to 12 months following transplantation and increased thereafter. The relative bone loss was greatest among group B patients (relative bone loss FN 3 months post-transplant: group A, 8% versus group B, 13%; P = 0.04). At 36 months, 8/17 group A and 2/9 group B patients had BMD levels that exceeded the pretransplant levels (P = 0.12). The early bone loss was positively correlated with an increase in resorption markers (s-1-CTP and u-Ntx). Group B had higher levels of both s-1-CTP and u-Ntx at 3 and 6 months post-transplant than group A patients (P = 0.03). Bone formation markers increased slowly from 6 months post-transplant and onwards. Relative bone loss was positively correlated to total glucocorticoid dose during the first 3 months post-transplant. There were no differences in BMD between patients receiving tacrolimus versus those receiving cyclosporin A. CONCLUSION: Bone loss following liver transplantation is considerable in patients with both cholestatic and non-cholestatic liver disease, the first group has the poorest starting-point while the latter group has the greatest bone loss following transplantation. Bone loss is closely correlated with biochemical markers of bone resorption and total dose of glucocorticoids given post-transplant.     

The Relationship Between Proton Pump Inhibitor Use and Longitudinal Change in Bone Mineral Density: A Population-Based From the Canadian Multicentre Osteoporosis Study (CaMos)

OBJECTIVES:Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk.METHODS:We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years.RESULTS:In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up.CONCLUSIONS:PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.     

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.     

Secondary Osteoporosis in Liver Transplant Recipients: a Longitudinal Study in Patients With and Without Cholestatic Liver Disease

Background: Metabolic bone disease is one of the major long-term complications in liver transplant recipients, but it remains unclear which patients are at highest risk for developing severe bone disease following transplantation. Methods: A total of 46 consecutive, adult patients with chronic liver disease accepted for a liver transplantation waiting list were prospectively included in the study. The patients were classified into two groups: group A—chronic cholestatic liver disease (n = 28), and group B—chronic non-cholestatic liver disease (n = 18). Bone mineral density (BMD) was measured at acceptance for the waiting list and at 3, 12 and 36 months following transplantation. Markers of bone turnover (serum-bone specific alkaline phosphatases (bALP), s-osteocalcin, s-l-collagen-C-terminal telopeptide (1-CTP) and urine N-terminal telopeptides u-Ntx) were measured at acceptance and at 3, 6, 12, 24 and 36 months following transplantation. BMD and markers of bone turnover were compared with similar values in a matched control group of 42 healthy individuals. Results: BMD decreased significantly during the early post-transplantation period (median bone loss femoral neck (FN) 3 months post-transplant 8.5%). BMD levels declined slightly from 3 to 12 months following transplantation and increased thereafter. The relative bone loss was greatest among group B patients (relative bone loss FN 3 months post-transplant: group A, 8% versus group B, 13%; P = 0.04). At 36 months, 8/17 group A and 2/9 group B patients had BMD levels that exceeded the pretransplant levels (P = 0.12). The early bone loss was positively correlated with an increase in resorption markers (s-1-CTP and u-Ntx). Group B had higher levels of both s-1-CTP and u-Ntx at 3 and 6 months post-transplant than group A patients (P = 0.03). Bone formation markers increased slowly from 6 months post-transplant and onwards. Relative bone loss was positively correlated to total glucocorticoid dose during the first 3 months post-transplant. There were no differences in BMD between patients receiving tacrolimus versus those receiving'cyclosporin A. Conclusion: Bone loss following liver transplantation is considerable in patients with both cholestatic and non-cholestatic liver disease, the first group has the poorest starting-point while the latter group has the greatest bone loss following transplantation. Bone loss is closely correlated with biochemical markers of bone resorption and total dose of glucocorticoids given post-transplant.