Long-lasting bone damage detected by dual-energy x-ray absorptiometry,phalangeal osteosonogrammetry,and in vitro growth of marrow stromal cells after allogeneic stem cell transplantation

Bone complications after allogeneic stem cell transplant (allo-SCT) include osteoporosis, fractures, and osteonecrosis. We investigated bone abnormalities in long-term survivors after busulfan cyclophosphamide-conditioning regimen, followed by human leukocyte antigen-identical sibling SCT. Bone density was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN) and phalangeal osteosonogrammetry (OSG) in 41 patients 1-10 yr after allo-SCT. Using colony-forming units-fibroblast (CFU-F) assay, we analyzed the repopulating capacity of clonogenic fibroblast progenitors belonging to the osteogenic stromal lineage. LS and FN bone mineral density (BMD) and phalangeal densitometric values were significantly reduced, compared with 188 healthy controls (P < 0.001). Decrease in T-score less than 1 SD was documented in 29% and 52% of patients at the LS and FN, respectively. OSG detected densitometric values with a T-score less than 1 SD in 68% of transplanted patients. The patients examined within the first 3 yr after transplant showed low BMD, which remained stable at FN and improved at LS. Phalangeal densitometry was low up to 10 yr after transplant. CFU-F was found permanently depressed and unable to give rise to a confluent stroma. Low serum osteocalcin levels were present throughout the whole follow-up period. A significant correlation was found between densitometric values detected by both techniques and CFU-F growth in vitro. Osteonecrosis was associated with lower FN BMD, and phalangeal densitometry correlated inversely with duration of amenorrhea and chronic graft vs. host disease requiring long-lasting steroid therapy. In conclusion, dual-energy x-ray absorptiometry and phalangeal OSG may provide complementary information on bone density after allo-SCT. Prolonged severe impairment of femoral BMD and phalangeal densitometry suggest that bone loss may persist for many years after transplant. Inability to regenerate a normal number of osteoblastic precursors in the stromal stem cell compartment may in part account for severe long-lasting posttransplant decrease in bone mass.     

Effects of calcium supplementation on bone loss and fractures in congestive heart failure

BACKGROUND: Cross-sectional studies have shown that more than 50% of patients with congestive heart failure (CHF) have decreased bone mineral density (BMD). There is limited knowledge about the longitudinal changes of BMD and how to treat bone loss in patients with CHF. METHODS: The present study was a prospective, longitudinal trial in which 33 male patients with CHF (ejection fraction (EF): 30+/-11%) were assigned to 1000 mg calcium supplementation or no supplementation. BMD was measured at the lumbar spine (LS) and the femoral neck (FN) by dual-energy X-ray absorptiometry at baseline and after 12 months. RESULTS: Osteopenia (LS 33% and FN 36%) and osteoporosis (LS 15% and FN 6%) were frequently seen in these patients; 70% showed impaired renal function, 42% secondary hyperparathyroidism, and 33% hypogonadism. Bone resorption markers were strongly elevated and correlated negatively with the EF. Patients without calcium supplementation revealed a reduction of BMD (LS 1.7% and FN 1.9%) within 12 months. The fracture incidence was 6%. Patients with calcium supplementation also demonstrated a 6% fracture incidence and a decrease in BMD (LS 1.2% and FN 1.6%), which was not significantly different from the untreated group. Loss of BMD at FN was only seen in patients with impaired renal function. CONCLUSIONS: Patients with CHF demonstrate a progressive decrease in BMD when compared with age-matched healthy individuals. Increased bone resorption due to renal insufficiency with consecutive secondary hyperparathyroidism is a main reason for BMD loss in CHF. Calcium supplementation alone cannot sufficiently prevent the decrease in BMD.     

Osteoporosis, mineral metabolism, and serum soluble tumor necrosis factor receptor p55 in viral cirrhosis

Liver cirrhosis is a risk factor for osteoporosis. Nevertheless, little is known about the mechanisms of bone mass loss in patients with viral cirrhosis. TNFalpha is a potent bone-resorbing agent. Serum concentrations of soluble TNF receptor p55 (sTNFR-55) correlate with clinical activity in liver cirrhosis. Our aim was to evaluate the possible role of sTNFR-55 in the pathogenesis of osteoporosis in patients with viral cirrhosis and its relationship with bone turnover markers. We studied 40 consecutive patients with viral cirrhosis and no history of alcohol intake and 26 healthy volunteers. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). Patients with viral cirrhosis had reduced BMD (expressed as the z-score) in all sites [LS, -1.5 +/- 0.22 (P < 0.001); FN, -0.37 +/- 0.15 (P < 0.01)]. Serum concentrations of sTNFR-55 and urinary deoxypyridinoline, a biochemical marker of bone resorption, were significantly higher in patients with osteoporosis than in patients without osteoporosis (P < 0.001 and P < 0.05, respectively). Serum levels of sTNFR-55 correlated inversely with BMD in LS (r = -0.62; P < 0.005) and FN (r = -0.47; P < 0.05) and positively with urinary deoxypyridinoline (r = 0.72, P < 0.001). Our findings show that high serum concentrations of sTNFR-55 play a role in the pathogenesis of viral cirrhosis-associated bone mass loss and provide evidence of increased bone resorption related to the high serum sTNFR-55 levels.     

Estrogen receptor genotypes and their association with the 10-year changes in bone mineral density and osteocalcin concentrations

We conducted a 10-yr prospective study of peak bone mass and its change in 604 women, aged 24-44 yr at study initiation, and related changes in bone mineral density (BMD) and osteocalcin (OCN) concentrations to estrogen receptor (ER) alpha gene polymorphisms in 442 of these women. We examined the association of ER alpha PvuII and XbaI polymorphisms with the 10-yr change in lumbar spine (LS) and femoral neck (FN) BMD, measured by densitometry, as well as serum OCN levels, after accounting for weight and menstrual status change. The women were members of the Michigan Bone Health Study, a population-based longitudinal study of BMD. There was a linear loss of LS BMD and curvilinear loss of FN BMD from peak bone mass over a 10-yr period. Women homozygous for the ER alpha gene variant without an XbaI restriction site (XbaI -/- genotype) had higher FN BMD and less change in LS over time. Women homozygous for the ER alpha gene variant without a PvuII restriction site (PvuII -/- genotype) had less LS BMD change over time as well as higher FN BMD. However, this higher FN BMD was dependent upon the rate of bone turnover as estimated from serum OCN change over time. The ER alpha genotype associations were statistically significant in explaining the rate of perimenopausal bone loss and its turnover; however, BMI or becoming postmenopausal contributed more to the magnitude of the difference in bone change.     

Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing's syndrome: a prospective, long-term study

OBJECTIVE: Endogenous Cushing's syndrome (CS) is associated with bone loss and an increased risk of fractures. However, the long-term outcome of treatment on bone health has not been adequately clarified. DESIGN: We followed 33 patients with active CS prospectively before and twice after treatment (mean follow-up 33 (n = 25) and 71 months (n = 18), respectively). The patients were compared to age-, sex- and body mass index (BMI)-matched controls, also followed longitudinally. METHODS: Bone mineral indices (bone mineral density (BMD), bone mineral content (BMC) and bone area) were evaluated in the lumbar spine (LS), femoral neck (FN), and total body (TB) by dual-energy X-ray absorptiometry (DXA). Biochemical markers of bone turnover were assessed by serum levels of osteocalcin and C-terminal telopeptides of Type-1 collagen (CTX-1). RESULTS: Mann-Whitney rank sum tests showed that BMD of the LS, FN and TB was reduced by 14.8% (P < 0.001), 15.7% (P < 0.001), and 9.2% (P < 0.001) in CS vs. controls at baseline, with markedly reduced serum osteocalcin (P = 0.014) and increased CTX-1 (P = 0.012) levels, but no correlation between markers. At first follow-up, BMD was increased in LS (7.9%, P < 0.001) and FN (3.5%, P = 0.003) compared to baseline. The time-dependent rise in BMD (LS (r = 0.59; P = 0.002) and FN (r = 0.52; P = 0.007); Spearman's rank correlation), in CS was paralleled by increased osteocalcin (275%, P < 0.001) and correlation between biochemical markers (r = 0.92, P < 0.001; Pearson's correlation). TB BMD did not increase significantly before the second follow-up, when BMD Z-scores were normalized in all three compartments. CONCLUSION: Our observations demonstrate restoration of coupled bone remodeling and normalization of bone mineral density in all measured skeletal compartments of treated CS patients after prolonged recovery, first significant in predominantly trabecular bone (i.e. lumbar spine).     

Osteoporosis and lung transplantation: a prospective study

STUDY OBJECTIVE: Osteoporosis is a well-recognized complication of lung transplantation that may significantly impair the quality of life of transplant recipients. We performed a prospective study of bone mineral density (BMD) before and after transplantation to determine the degree of bone mass loss associated with lung transplantation Patients and design: We conducted a prospective study of BMD in 28 patients with various end-stage respiratory diseases pretransplantation and 6 to 12 months posttransplantation. The BMD of the lumbar spine (LS) and femoral neck (FN) were measured. All 28 patients were treated only with vitamin D and calcium supplementation posttransplant. The primary endpoint was the percentage change in BMD. The secondary endpoint was the incidence of fractures posttransplant. A univariate analysis was conducted to determine the various risk factors associated with bone mass loss pretransplant and posttransplant. RESULTS: Prior to transplantation, moderate to severe bone disease was evident. The mean (+/- SD) pretransplant T score (the number of SDs from the peak bone mass) and Z score (the number of SDs from the age-matched mean) for the LS were -1.72 +/- 1.37 and -1.44 +/- 1.31, respectively. The mean pretransplant T score and Z score for the FN were -2.65 +/- 1.01 and -1.5 +/- 1.43, respectively. Within 6 to 12 months posttransplant, the mean BMD for the LS decreased by 4.76% (p < 0.001), while the mean BMD for the FN decreased by 5.3% (p < 0.001). Five of the 28 patients (18%) suffered osteoporotic fractures posttransplant, while no fractures were documented pretransplant. The cumulative steroid dose posttransplant was associated with a drop in BMD for the LS and FN (r = 0.39, p = 0.039 and r = 0.63, p < 0.001, respectively), while a negative association was found between cumulative steroid use pretransplant and baseline LS and FN T scores (r = -0.4, p = 0. 02 and r = -0.43, p = 0.023, respectively). CONCLUSION: Within 6 to 12 months after lung transplantation, there is a significant decrease in BMD at both the LS and FN levels (approximately 5%) despite vitamin D and calcium supplementation. This drop in BMD is associated with a relatively high incidence of osteoporotic fractures posttransplant.     

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.     

High prevalence of early-onset osteopenia/osteoporosis after allogeneic stem cell transplantation and improvement after bisphosphonate therapy

Osteopenia/osteoporosis (O/O) has been associated with allogeneic stem cell transplantation (alloSCT). We retrospectively reviewed 102 patients undergoing a first alloSCT from 2000 to 2005 at our center to evaluate the prevalence of O/O < or =6 and >6 months post-alloSCT. Fifty-six patients did not have a dual energy X-ray absorptiometry (DXA) scan following alloSCT. Approximately half (n=13/27) of those with a first DXA scan < or =6 months post-alloSCT had O/O and a similar rate (n=9/19) was seen in those with a first DXA scan >6 months. There were no significant differences in patient characteristics between the normal and O/O groups. The dual femur (DF) appeared to be more vulnerable to alloSCT-induced bone mineral density (BMD) loss than the lumbar spine (LS), regardless of screening time. O/O patients were treated with bisphosphonates and 41% had a repeat DXA scan post-treatment. No patient developed jaw osteonecrosis and significant BMD improvement was seen at the LS (mean BMD, 1.03+/-0.13 vs 1.08+/-0.12, P=0.004) but not the DF (mean BMD, 0.84+/-0.06 vs 0.85+/-0.08, P=0.29), indicating BMD loss at the DF is more resistant than the LS to antiresorptive therapy. Our results demonstrate that O/O is an early and late complication post-alloSCT and bisphosphonate treatment reverses BMD loss at the LS.     

Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection

AIM: Previous studies suggest that loss of bone mineral density (BMD) frequently occurs in patients with chronic viral liver disease, presenting with histologically proven liver cirrhosis. However, little is known about the occurrence of bone disease in non-cirrhotic patients with chronic hepatitis B or C. Therefore, it was the aim of this study to evaluate this particular population for BMD and bone turnover markers. METHODS: Biochemical markers of bone turnover and BMD were measured in 43 consecutive patients with HCV (n = 30) or HBV (n = 13) infection without histological evidence for liver cirrhosis. Mean age was 49 years (range 26-77 years). BMD was measured by dual X-ray absorptiometry in the femoral neck (FN) and the lumbar spine (LS) region. In addition, bone metabolism markers were measured. RESULTS: BMD was lowered in 25 (58%) of the patients with chronic hepatitis B or C (FN; 0.76 (0.53-0.99); LS: 0.96 (0.62-1.23) g/cm2). Eight (32%) osteopenic patients were diagnosed with osteoporosis. Bone-specific alkaline phosphatase (P= 0.005) and intact parathyroid hormone (iPTH) (P = 0.001) were significantly elevated in the more advanced stages of fibrosis. Mean T-score value was lower in patients with chronic hepatitis C as compared to patients suffering from chronic hepatitis B; however, the difference was not statistically significant (P= 0.09). CONCLUSION: There was a significantly reduced BMD in non-cirrhotic patients with chronic hepatitis B or C infection. Alterations of bone metabolism already occurred in advanced liver fibrosis without cirrhosis. According to our results, these secondary effects of chronic viral hepatitis should be further investigated.     

Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction

Since bone pathology is a major concern in type 1 Gaucher disease (GD1), we evaluated bone mineral density (BMD) in adults receiving velaglucerase alfa in the seminal Phase I/II and extension trial. Ten treatment-na?ve symptomatic patients with GD1 (four men, six women; median age 35years, range 18-62years) were included; of these, four patients were receiving bisphosphonates at enrollment. Using WHO criteria to classify the lumbar spine (LS) and femoral neck (FN) BMD T-scores, respectively, one (10%) and four (40%) patients had osteoporosis; eight (80%) and five (50%) had osteopenia; and one each (10%) was in the normal range, at baseline. By Month 69, two LS and one FN osteopenic patients normalized and one FN osteoporotic patient became osteopenic; change was seen only in patients not receiving bisphosphonates. Significant improvements in BMD Z-scores were seen at the LS by Month 24 and at the FN by Month 33 and were continuous thereafter. In linear mixed models, Z-scores were significantly lower than the reference population at baseline and improved significantly with treatment (LS and FN both P<0.01); analysis of the subgroup of patients not receiving bisphosphonates showed similar results. In conclusion, in this small cohort, velaglucerase alfa was associated with clinically meaningful and statistically significant LS and FN BMD improvements as early as Month 24 (LS) and 33 (FN), despite dose reduction and significant baseline skeletal pathology. These results suggest that velaglucerase alfa may hold promise in the management of skeletal pathology associated with GD1.     

Bone mineral density progression following long-term simultaneous pancreas-kidney transplantation in type-1 diabetes

IntroductionSimultaneous pancreas-kidney transplantation (SPKT) has demonstrated favorable impact on the progression of chronic complications in type-1 diabetes (T1D) and terminal chronic kidney disease (CKD). However, some CKD mineral and bone disorders (CKD-MBD) may persist, even after transplantation. There are only a few studies addressing the long-term progression of bone mineral density (BMD) in these patients. Our aim was to assess baseline BMD and long-term progression and consequences in patients with T1D undergoing SPKT.MethodsA retrospective cohort included patients undergoing SPKT in our tertiary center between 2000 and 2017. BMD progression was assessed on dual X-ray absorptiometry (DXA). Only patients with baseline data and a minimum follow-up of 2 years were included.ResultsSeventy-three patients were included, 53.4% male, with a median age at SPKT of 35 years (interquartile range [IQR] 31; 39). At transplantation, the median T-scores for the lumbar spine (LS) and femoral neck (FN) were −1.6 (IQR −2.6; −1.1) and -−2.1 (IQR −2.7; −1.6), respectively. Seventy-five percent of patients presented low BMD (osteopenia or osteoporosis) in the LS and 90% in the FN, with 33% osteoporosis in the LS and 36% in the FN. On multivariate analysis, male gender (odds ratio [OR] 10.82, 95% confidence interval (CI) 2.88–40.70) and low body-mass index (BMI) (OR 0.73, 95% CI 0.55–0.97) were significantly associated with lumbar but not femoral osteoporosis. At long-term follow-up, BMD significantly improved in the LS (ΔT-score +0.41, P < 0.001) and FN (ΔT-score +0.29, P = 0.01), at a median 4 years after SPKT. Twelve (16.4%) and 9 (12.3%) patients showed persistent FN and LS osteoporosis, respectively. Multivariate linear regression showed that high BMI was predictive of improvement in BMD.ConclusionsThis study demonstrated severe skeletal fragility in T1D patients with terminal CKD undergoing SPKT, more than a quarter of whom showed osteoporosis. The significant improvement in BMD may result from metabolic correction by SPKT and from physiological skeleton mineralization, which continues in this age group. BMD progression was positively associated with BMI, due to improved nutritional balance after transplantation.     

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation

Ovarian failure after allogeneic stem cell transplant (allo-SCT) is an important risk factor for development of osteoporosis. We investigated the effects of various antiresorptive treatments in long-term surviving females with ovarian failure after allo-SCT. A total of 60 women with osteoporosis or osteopenia were divided randomly into four groups of 15 women each. Group 1 was treated with calcium and vitamin D alone, group 2 received the same treatment in combination with hormone replacement therapy (HRT), group 3 received risedronate (35 mg weekly, orally for 1 year) and group 4 zoledronic acid (3 monthly doses of 4 mg (intravenous)). All groups were similar for age, body mass index, underlying disease and time elapsed from transplant. Lumbar and femoral bone mineral density (BMD) were measured at baseline and after 12 months, together with serum osteocalcin and urinary hydroxyproline. At 12 months, a significant decrease in lumbar and femoral BMD was observed in group 1 and a milder decrease in group 2. Risedronate treatment increased significantly lumbar BMD and prevented bone loss at the femoral neck. Zoledronic acid increased significantly both lumbar and femoral BMD. In groups 3 and 4 the hydroxyproline excretion was significantly reduced, while osteocalcin mildly increased only in group 4. In conclusion, bisphosphonate administration is useful to prevent and treat bone demineralization in young adult women after allo-SCT.     

Factors influencing bone loss in rheumatoid arthritis: a longitudinal study

OBJECTIVES: To assess the occurrence of bone loss in rheumatoid arthritis (RA) and to determine the factors influencing bone loss (particularly the usefulness of bone turnover markers) over an 18-month period. METHODS: A total of 51 patients were studied, 6 men and 45 females (of whom 35 were menopausal). Their mean age was 56 +/- 10 years and the mean RA duration was 12 +/- 10 years. Twenty-eight (55%) were receiving corticosteroids (10 mg/day for a mean duration of 6 +/- 5 years). Several clinical and biological parameters reflecting disease activity or severity were recorded both at the 0 and 18-month investigations. Bone turnover was assessed at baseline by measuring the serum levels of 4 biological markers. Three of them reflected bone formation, i.e., procollagen type I C-terminal propepeptide (PICP), procollagen type I N-terminal propeptide (PINP) and osteocalcin (OC). The fourth, procollagen type I-C terminal telopeptide (ICTP), reflected bone resorption. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry both at the lumbar spine (LS) and femoral neck (FN) at baseline and 18 months later. RESULTS: Bone loss occurred both at the LS: 2.1%, [95% CI: 0.8%-3.4%, P < 0.005] and femoral neck: 3.1%, [95% CI: 1.1%-5.1%, P < 0.005]. Bone loss was markedly increased for postmenopausal women at the FN: 5.3% [95% CI: 2.9%-7.6%, P < 0.005]. Bone loss was not statistically significantly different between users and non-users of steroids. Bone loss at the LS was significantly correlated with both osteocalcin (r = 0.51, P < 0.01) and ICTP levels (r = 0.32, P < 0.05). FN bone loss was correlated with the osteocalcin level only (r = 0.34, P < 0.05). Fast losers (bone loss at the LS above the median) had higher OC (P < 0.01) and ESR (P < 0.05) levels at baseline as compared with slow losers (bone loss at the LS below the median). CONCLUSION: Bone loss occurs in RA particularly at the FN and seems to be influenced by increased bone turnover and high levels of inflammation.     

Calcium-parathyroid hormone-vitamin D axis and metabolic bone disease in chronic viral liver disease

BACKGROUND: The main process involved in hepatic osteodystrophy seems to be osteoporosis, but decreased 25-hydroxylation of vitamin D might lead to osteomalacia and secondary hyperparathyroidism. METHODS AND RESULTS: We studied bone mineral density (BMD) by using DEXA-Expert Lunar, biochemical markers of bone turnover and calcium-parathyroid hormone (PTH)-vitamin D axis in 100 patients with chronic viral hepatitis secondary to hepatitis C virus: 49 non-cirrhotic (NCir) and 51 with cirrhosis (Cir) confirmed by liver biopsy and/or clinical and biochemical features. When compared to the age-matched population, 25% of the patients had low BMD at the lumbar spine (LS), 26.2% at Ward's triangle, 15.5% at the femoral neck (FN), and 20.2% at the trochanter. No difference was found either between Cir and NCir groups or between sexes. Urinary N-telopeptide was increased in 31.86% of the patients, and negatively correlated with BMD at the LS and trochanter (P < 0.02). Serum bone-specific alkaline phosphatase was elevated in 21% of the patients and negatively correlated with BMD at the trochanter and Ward's triangle (P < 0.02). Fasting 25-hydroxyvitamin D was low in only three Cir patients, with no difference between the Cir and NCir groups, but it was higher in men (51.8 +/- 16.0 ng/mL) compared to women (40.4 +/- 14.4 ng/mL; P = 0.001). Fasting serum calcium was lower in Cir than NCir patients, P = 0.019. Fasting intact PTH was elevated in 42% of the patients, but the mean serum levels were similar in Cir and NCir groups. CONCLUSION: We found no evidence of vitamin D deficiency, but cannot exclude the participation of PTH in the high bone turnover and bone loss in the population with chronic viral hepatitis.     

Long-term follow-up of bone mineral density in Addison's disease

BACKGROUND AND AIMS: There is conflicting evidence regarding the long-term effects of long-term glucocorticoid replacement therapy (GRT) on bone mineral density (BMD) in patients with chronic adrenal insufficiency. Our aim was to evaluate bone turnover and changes in BMD in patients on GRT. PATIENTS AND METHODS: We have studied 25 subjects (six men, 19 women; aged 62.4 +/- 11.3 years, duration of disease 21.7 +/- 11.7 years, fasting cortisol 63 +/- 36 nmol/l) on GRT (hydrocortisone 30 mg/day or prednisone 7.5 mg/day). BMD was assessed at the lumbar spine (LS; L2-L4), proximal femur (PF) and ultra distal radius (UR) by dual energy X-ray absorptiometry (DXA). The rates of bone loss were calculated using previous DXA measurements at the LS (48 and 60 months earlier). Serum calcium, phosphate alkaline phosphatase (ALP), bone ALP, serum osteocalcin (BGP), intact parathyroid hormone (PTH) and 25(OH) vitamin D were also measured. RESULTS: BMD [Z-score; 95% confidence interval (95% CI)] was normal at the LS: (-1.15-+0.07); PF: (-0.90-+0.22) and UDR (-0.77-+0.36). No significant differences were found according to the type of replacement therapy or sex. No significant bone loss (g/cm2; 95% CI) was detected at the LS: (-0.021-+0.023). Fifty-six per cent of patients met osteoporotic criteria; a greater proportion of patients treated with prednisone had osteoporosis compared with those an hydrocortisone. All bone markers were in their normal ranges. CONCLUSIONS: Patients on long-term therapy do not show accelerated bone loss at the lumbar spine. Nevertheless, a considerable proportion of patients, mainly those treated with prednisone, showed densitometric osteoporosis.     

Hormonal and biochemical parameters in the determination of osteoporosis in elderly men.

The extent to which changes in several hormonal and biochemical parameters are involved in the pathogenesis of osteoporosis in men remains controversial. This study examined the roles of free testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), 25-hydroxyvitamin D, PTH, and insulin-like growth factor I in the determination of bone mineral density (BMD) in 437 community-dwelling elderly men. Age, height, weight, quadriceps strength, and femoral neck (FN) and lumbar spine (LS) BMD were also obtained. In multiple regression analysis, after adjusting for age and weight, low E2 (P = 0.01), and high SHBG (P = 0.0002) levels were common determinants of FN and LS BMD. In addition, high PTH (P = 0.03) was an independent predictor of FN BMD, and low free T (P = 0.02) was an independent predictor of LS BMD. Low free T was associated with FN BMD in univariate analysis only. The hormonal measurements collectively accounted for 5% and 7% of the age- and weight-adjusted variance of FN and LS BMD, respectively. The sex steroids, SHBG and insulin-like growth-I were found to be interrelated using a technique of path analysis that examines the intercorrelation between these variables. A subject with any one abnormal serum parameter had a 4-fold increase in the risk of osteoporosis, whereas three abnormal parameters were associated with an 11-fold increased risk, although the latter group only applied to 1% of the study population. Although the precise causal effects these biochemical parameters may have on the development of osteoporosis remains to be determined, the present findings support an important interrelated role for these hormonal and biochemical parameters on changes in bone density in elderly men.     

Bone mineral density in Crohn's disease: a longitudinal study of budesonide,prednisone, and nonsteroid therapy

OBJECTIVE: Corticosteroids may contribute to the bone loss associated with Crohn's disease (CD). We investigated the effect on bone mineral density (BMD) of treatment with budesonide, a steroid with low systemic activity, and compared the outcome with prednisone and nonsteroid therapy in patients with CD. METHODS: Prospective annual BMDs of the lumbar spine (LS) and femoral neck (FN) were measured for 2 yr in 138 patients with quiescent CD treated with mean daily doses of 8.5 mg of budesonide (n = 48), 10.5 mg of prednisone (n = 45), or nonsteroid drugs (n = 45). RESULTS: Between baseline and 1 yr, the mean LS BMD decreased 2.36% in the budesonide group (p < 0.001), 0.61% in the prednisone group (ns), and 0.09% in the nonsteroid group (ns). The difference between budesonide and nonsteroid groups was significant (p = 0.003). In the 2nd yr, LS BMD did not change in the three groups. After 2 yr, FN BMD decreased 2.94% in the budesonide group (p < 0.01), 0.36% in the prednisone group (ns), and 1.05% in the nonsteroid group (ns); the differences among groups were not significant. The proportion of patients with bone loss of >2% per annum at the LS and FN was higher in the budesonide group than in the nonsteroid group (p < 0.001) and prednisone group (p < 0.05). CONCLUSIONS: Patients with CD receiving maintenance treatment for 2 yr with prednisone show little change in BMD, whereas treatment with budesonide may be associated with LS and FN bone loss. Budesonide does not confer an advantage over low-dose prednisone for the preservation of BMD.     

The use of parenteral clodronate in elderly women with postmenopausal osteoporosis: compliance,effects on bone mineral density and on bone turnover

The aim of the study was to evaluate parenteral clodronate (CLD) compliance in patients with postmenopausal osteoporosis and intolerance to aminobisphosphonates. Moreover, we have also assessed the effects of CLD on bone mineral density (BMD) and bone turnover. Eighty-four consecutive postmenopausal women with osteoporosis (range 62-74 years) were enrolled and randomly allocated to three groups: group A included 26 women who received CLD i.v., 300 mg/2 weeks and oral supplemental calcium carbonate (500 mg x 2/day) and vitamin D3 (400 IU x 2/day); group B included 28 women who received CLD i.m., 100 mg/week, and the same dose of calcium and vitamin D3 administered to group A; group C, the control group, included 30 women receiving only calcium and vitamin D3 at the same doses as the other two groups. The lumbar spine (L1-L4) and femoral neck (FN) BMD were measured by dual energy X-ray absorbiometry at time 0 (T0) and after 6 (T6), 12 (T12), 18 (T18) and 24 (T24) months. At the same time, the serum bone specific alkaline phosphatase and amino-terminal telopeptide of type I collagen normalized by creatinine (NTx/cr) were determined at T0, T6, T12, T18, and T24. Eighty (95.2%) women completed the study, 24 in group A, 27 in group B and 29 in group C. In groups A and B, after 6 months of treatment we found a significantly greater (p < 0.05) increase in the L1-L4 BMD with respect to group C. After 12 months of therapy, in group A the L1-L4 BMD (1.8 +/- 0.5%) was significantly higher (p < 0.05) than that in group B (0.9 +/- 0.3%). At the end of the study, in groups A (1.2 +/- 0.5%) and B (1.1 +/- 0.4%) the percentage increase in the FN BMD was significantly greater (p < 0.05) than in group C (0.6 +/- 0.5%). After 24 months of therapy, there was no difference in the FN BMD between groups A and B. Since the sixth month, both the bone specific alkaline phosphatase and NTx/cr were found to be more markedly and significantly decreased (p < 0.05) in groups A and B with respect to group C. After 18 months, in group A (NTx/cr -16.7 +/- 0.8%) we observed a significantly reduced (p < 0.05) bone resorption with respect to group B (NTx/cr -11.0 +/- 0.5%). In group B, only 3 patients (11.2%) referred pain at the site of drug administration. Our data demonstrate that compliance to parenteral CLD is satisfactory and that this drug reduces bone turnover, increases the L1-L4 BMD and decreases the FN BMD loss. Parenteral CLD administration can represent an effective alternative treatment for postmenopausal women with osteoporosis, especially those who do not tolerate oral aminobisphosphonates.     

Pretransplantation bone disease in patients with primary pulmonary hypertension

INTRODUCTION: Osteoporosis is a common condition in patients with end-stage lung disease, but little attention has been given to bone disease in patients with primary pulmonary hypertension (PPH). The purposes of this study were as follows: (1) to determine the prevalence of osteoporosis in patients with severe PPH before lung transplantation, (2) to investigate whether generally accepted risk factors for osteoporosis would play a role in this special group of patients, and (3) to determine whether there is an association between functional parameters and pretransplantion bone mass. DESIGN: A retrospective analysis of 18 consecutive patients with PPH accepted for lung transplantation at the University Hospital of Zurich. MEASUREMENTS AND RESULTS: Decreased bone mineral density (BMD) [T score <- 1.0] was found in 11 of 18 patients (61%) at the femoral neck (FN) and 13 of 18 patients (72%) at the lumbar spine (LS). We did not find a significant difference of BMD in a gender- or age-specific manner. Body mass index (BMI) correlated significantly with BMD and T score at the FN and WT. Pulmonary vascular resistance (PVR) was notably linked with BMD at the FN. We found a positive association between walking distance in the 12-min walking test and BMD at the FN and WT. CONCLUSIONS: Low bone density is a very frequent condition in patients with severe PPH. In contrast to the general population, in our study group neither age nor female gender were significantly associated with lower bone mass. Body weight and BMI were highly coupled with BMD. Among the functional parameters, walking distance and PVR were correlated to BMD at the FN. Considering that patients with PPH may have an improved life expectancy in the future, the early diagnosis, prevention, and treatment of osteoporosis should receive high priority.     

Bone mineral density in women with systemic lupus erythematosus

The aim of this cross-sectional study was to determine the prevalence of reduced bone mineral density (BMD) in a group of female SLE patients and to identify factors predictive of reduced BMD. Femoral neck (FN) and lumbar spine (LS) dual-energy X-ray absorptiometry results were evaluated in 79 pre- and postmenopausal women with SLE aged (mean, range) 49 (22–73) years). Variables evaluated were disease duration, SLEDAI, current and cumulative corticosteroid dose, Steinbrocker’s functional classification, use of immunosuppressive agents, and history of fracture due to minor trauma. A T-score of ≤1.0 was found in 61.9% at the LS and 48.3% at the FN, and 18 (23.7%) patients belonged to the category of osteoporosis at LS, compared to only three (5.4%) patients at FN. A statistical difference (P= 0.014) was found when comparing LS BMD in pre- and postmenopausal patients. LS BMD had a significant correlation with daily and cumulative steroid dose (P= 0.016 and 0.031, respectively). There was a significant difference in LS BMD between the daily steroid dose group receiving ≤7.5 and those receiving >7.5 mg/day (P= 0.008), and also in FN BMD comparing groups on 0 and >7.5 mg/day (P= 0.022). There was significant difference in LS and FN BMD between patients in Steinbrocker classes I and III (P= 0.016 and 0.005, respectively). No significant correlation was found in either subgroup between BMD and other studied parameters. We concluded that the prevalence of reduced bone mass at LS is pronounced among postmenopausal women with SLE, in those with a high Steinbrocker functional classification and those on a high daily steroid dose. Therefore, these patients should be considered as a high-risk group deserving regular spinal BMD scans and therapy in time to prevent vertebral fractures. Received: 26 March 2000 / Accepted: 18 September 2001