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.     

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.     

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.     

Bone loss in patients with inflammatory bowel disease is less than expected: a follow-up study.

BACKGROUND: In spite of the accumulating evidence of an increased prevalence of osteopenia and osteoporosis in patients with inflammatory bowel diseases (IBD), the time course of bone loss is not well described, and there is little knowledge about factors indicating an increased risk of rapid bone loss. METHODS: We conducted a follow-up study in 80 IBD patients (45 men and 25 premenopausal and 10 postmenopausal women), 19 with ulcerative colitis and 61 with Crohn disease, with a mean follow-up time of 568 +/- 60 days, to assess bone loss, risk factors of rapid bone loss, and value of bone markers to predict bone loss. Bone mineral density was measured by dual-energy X-ray absorptiometry, bone formation by bone alkaline phosphatase (BAP), and bone resorption by N-terminal telopeptide of type-I collagen (NTX) and free deoxypyridinoline (DPD). RESULTS: Bone density changes per year were 0.46% +/- 3% at the spine, 0.06% +/- 5.1% at the femoral neck, -1.1% +/- 7.7% at the triangle of Ward, and -0.52% +/- 1.86% at total body level. Type and duration of disease, sex, age, and level of NTX, DPD, and BAP at base line did not show significant differences between patients who lost and those who did not lose bone mass. Bone loss was significantly higher in patients with (n = 28) than in those without steroids (n = 52) at the femoral neck and Ward triangle but not at the spine and total body. CONCLUSIONS: Change in bone mass in IBD patients during short-term follow-up is low on average, but there is great heterogeneity within the population, which cannot be explained by the use of steroids alone. Bone loss cannot be predicted by analysis of bone markers.     

GnRH类似物治疗对男性前列腺癌患者骨丢失的影响

目的探讨GnRH类似物治疗对老年男性前列腺癌患者骨量丢失、骨转换及身体成分的影响。方法确诊前列腺癌患者33人,同年龄健康男性35人,分别在治疗前、治疗12个月后测定受试者腰椎24（L2-4）、左股骨颈（FN）、全髋（Total Hip）的骨密度及全身总骨量、体脂（Total fat mass）和肌肉（Total lean mass）含量,并检测血清骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）、250HD、尿Ⅰ型胶原C端交联物（CTX）等骨转换指标。结果前列腺癌GnRH类似物治疗组和对照组相比基线水平的骨密度和骨代谢各项指标间都没有显著性差异,GnRH类似物治疗12个月后,血FSH、T、E2分别下降了66．0％、87．5％和75．0％（P〈0．01）,血PSA水平下降100％（P〈0．001）;腰椎、股骨颈、全髋及全身骨量丢失率分别为-2．05％、-3．55％、-3．47％和-3．64％,与对照组相比各部位骨量的下降均有显著性差异（P〈0．05）;Total fat mass和Total lean mass变化率分别为＋12．6％和-10．8％,与对照组相比lean mass下降具有显著性差异（P〈0．05）;尿CTX／Cr和血250HD变化率分别为＋54．71％和-43．75％,与对照组相比变化率有显著性差异（P〈0．05）。6个月时骨转换标记物尿CTX／Cr的变化率与12个月时骨丢失率呈负相关。结论前列腺癌患者接受GnRH类似物治疗后出现明显的骨转换加速、骨量丢失增加及身体脂肪肌肉成分的改变,对这些病人及时监测骨密度和骨转换指标有利于早期诊断早期防治。     

High habitual calcium intake attenuates bone loss in early postmenopausal Chinese women: an 18-month follow-up study

This study assessed the association of habitual dietary calcium intake and bone loss in early postmenopausal women. Four hundred fifty-four healthy postmenopausal Chinese women were enrolled for this 18-month cohort study. The subjects were 48-62 yr of age and within 12 yr of natural menopause. Dietary intake was assessed by the food frequency method, and bone mass was measured using dual energy x-ray absorptiometry at baseline and 9 and 18 months. The association between mean habitual dietary intake over the follow-up period and the rate of bone loss was examined. During the 18-month follow-up, the total loss rates of BMD at the whole body, lumber spine, femoral neck, and total hip were 1.28, 0.60, 1.54, and 0.56% (all P < 0.01). Subjects were stratified into four quartiles according to calcium intake during the period of follow-up. Quartiles I-IV had median intakes of 341, 505, 682, and 934 mg Ca/d. Subjects in quartile IV had significantly less BMD loss at the whole body and less BMD/bone mineral content loss at Ward's triangle, even after adjustments for confounding factors (by analysis of covariance). Multiple linear regression analyses showed significant positive associations between calcium intake and BMD change at the whole body (P = 0.006) and Ward's triangle (P = 0.021). Calcium intake was significantly associated with bone mineral content change at the trochanter (P = 0.025) and Ward's triangle (P < 0.001). No significant effect of calcium intake at the spine was found. In conclusion, habitual dietary calcium intake had a beneficial effect on bone loss at the whole body and some regions of the hip. Our findings suggest that an intake exceeding 900 mg calcium/d was helpful in the prevention of cortical bone loss among early postmenopausal Chinese women.     

Increases in bone mineral density after discontinuation of daily human parathyroid hormone and gonadotropin-releasing hormone analog administration in women with endometriosis

Intermittent PTH administration increases spinal bone mineral density (BMD) and prevents bone loss from the hip and total body in young women treated with a long acting GnRH analog for endometriosis. To establish whether these beneficial effects on BMD persist after PTH administration is discontinued, we remeasured BMD and biochemical markers of bone turnover in 38 women with endometriosis who had been treated with a GnRH analog alone (nafarelin acetate; 200 microg, intranasally, twice daily; n = 23; group 1) or who had received nafarelin plus human PTH-(1-34) (40 microg/day, s.c.; n = 15; group 2) for 6-12 months 1 yr after therapy was completed. Cyclic menstrual function returned promptly after nafarelin therapy was discontinued. In group 1, BMD increased significantly at all sites [P < 0.001 for the anterior-posterior (AP) and lateral spine; P = 0.014 for the femoral neck; P = 0.004 for the trochanter], except the proximal radius (P = 0.065) and total body bone density (P = 0.069) after nafarelin therapy was stopped. In group 2, BMD increased significantly at the AP spine (P < 0.001), lateral spine (P = 0.012), femoral neck (P = 0.002), and trochanter (P = 0.029) after nafarelin therapy was stopped. BMD of the spine in the AP projection increased more in group 2 and than in group 1 after therapy was stopped (P = 0.045). Despite these increases after discontinuation of nafarelin therapy, BMD was still significantly below baseline values at the AP spine (P < 0.001) and femoral neck (P = 0.006) and tended to be lower than baseline values at the trochanter (P = 0.057) and total body (P = 0.101) at the end of the 1-yr follow-up period in group 1. In contrast, BMD was significantly above baseline values at the AP and lateral spine (P < 0.001) sites and was similar to baseline values at the other skeletal sites at the end of the 1-yr follow-up period in group 2. Bone turnover returned to baseline values in both groups when therapy was stopped. We conclude that the beneficial effects of PTH on bone persist in women who regain cyclic menstrual function. Although part of the increases in BMD are probably due to restoration of ovarian function, additional increases in BMD most likely represent a further anabolic effect of PTH on bone that is not detected until after PTH administration is stopped.     

A randomized controlled trial of estrogen replacement therapy in long-term users of depot medroxyprogesterone acetate

Long-term use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA, Depo-Provera) is associated with a reduction in bone mineral density (BMD), particularly in the lumbar spine. The cause of DMPA-associated bone loss is not known, but the relative estrogen deficiency induced by DMPA use could be responsible. We have undertaken a randomized, double-blind controlled trial of oral estrogen replacement therapy in 38 premenopausal women (mean age 37) with a minimum 2 yr DMPA use who had a below average baseline lumbar spine BMD (T score < or = 0). Nineteen women were allocated to receive conjugated estrogens (0.625 mg/d orally) and 19 to receive a matching placebo. All continued with regular DMPA injections throughout the study. Areal bone density was measured by dual energy x-ray absorptiometry at the lumbar spine, femoral neck, and total body sites every 6 months for 2 yr; the main outcome measure being the change in areal BMD at the lumbar spine. At baseline, the two groups were well matched for demographic, anthropometric, and biochemical variables, and for BMD. Twenty-seven subjects completed at least 18 months in the study, and 26 the full 2 yr, with similar numbers dropping out from each group (mainly for personal reasons). In the estrogen-treated group, mean lumbar spine BMD increased 1%, whereas in the placebo group it fell 2.6%, over 2 yr. The between group differences were 2.0% at 12 months (P = 0.058), 3.2% at 18 months (P < 0.01), and 3.5% at 24 months (P < 0.002). Differences of lesser statistical magnitude were seen at the femoral neck (between group differences at 2 yr: 2.7%, P = 0.24), Ward's triangle (5.0%, P = 0.055), greater trochanter (3.6%, P = 0.056), total body (1.3%, P = 0.046), legs (1.3%, P = 0.065), and trunk (2.0%, P = 0.029). There were no major adverse events. These data support the view that the likely cause of DMPA-associated bone loss is estrogen deficiency and demonstrate that it can be arrested by estrogen replacement therapy.     

Age-Related Bone Mineral Density Patterns in Koreans (KNHANES IV)

Context: Bone loss is considered to begin with menopause in women and later in life in men; however, several recent studies have reported that bone loss began in young adults. There are still discordant results concerning age-related changes in bone mineral density (BMD), especially in nonvertebral bone. Objective: The objective of the study was to investigate the age-related changes in BMD in Korean youth. Design and Setting: This was a population-based, cross-sectional study from the Fourth Korea National Health and Nutrition Examination Surveys. Participants: A total 10,575 Korean (4,731 males and 5,844 females) aged 10-80 yr were included. Main Outcome Measures: BMD at the spine and hip was measured using dual X-ray absorptiometry. Results: Age-related bone loss at the femoral neck in males occurred continuously with temporary acceleration phase after achieving peak bone mass (PBM). In contrast, age-related bone loss at total hip in both sexes and femoral neck in females showed three obvious phases: acceleration, consolidation, and then the second acceleration phase after reaching PBM. Interestingly, this pattern of bone loss was more significant in the total hip and thus showed the acceleration phase until the late 20s and the consolidation phase until the late 40s. Early accelerated loss of BMD was not observed at the lumbar spine in each sex. Although body mass index and body fat percentage were more related with BMD than other clinical parameters, they could not explain the early accelerated loss of BMD at the femur. Conclusions: There was an accelerated bone loss at the femur in both sexes during early adulthood and more than 60% of the bone loss before age 50 yr occurred during this period.     

Androgens and bone density in women with hypopituitarism

Hypopituitarism is associated with osteopenia and a reduction in lean body mass. We have recently demonstrated markedly reduced serum androgen levels in women with hypopituitarism. We hypothesized that serum androgen levels and lean body mass are important determinants of bone mineral density (BMD) in women with hypopituitarism. In addition, because IGF-I may stimulate androgen secretion in women, we investigated whether GH administration results in an increase in serum androgen levels. Sixteen women with a history of pituitary disease of adult-onset and serum GH levels less than 5 ng/ml on stimulation testing underwent BMD and body composition testing by dual-energy x-ray absorptiometry. Univariate regression analysis revealed strong correlations between androgen levels and BMD [lateral spine BMD and dehydroepiandrosterone sulfate (DHEAS) (r = 0.68, P = 0.03), total hip BMD and free T (r = 0.60, P = 0.01), Ward's triangle BMD and DHEAS (r = 0.68, P = 0.004), Ward's triangle BMD and free T (r = 0.54, P = 0.03), femoral neck BMD and free T (r = 0.52, P = 0.04), and femoral neck BMD and DHEAS (r = 0.51, P = 0.04)]. When adjusted for age using Z scores, correlations at the femoral neck no longer reach significance. Correlations between androgens and BMD at other sites, including anterior-posterior spine and total body, were not significant, and neither total T nor androstenedione correlated with BMD at any site. Lean body mass strongly correlated with BMD [total hip (r = 0.80, P = 0.0002), total body (r = 0.78, P = 0.0003), trochanter (r = 0.74, P = 0.001), Ward's triangle (r = 0.56, P = 0.02), femoral neck (r = 0.53, P = 0.04), and anterior-posterior spine (r = 0.52, P = 0.04)]. In stepwise regression models, DHEAS determined 47% of the variation in Ward's triangle BMD (R(2) = 0.47, P = 0.004) and 46% of lateral spine BMD (R(2) = 0.46, P = 0.03). Lean body mass determined 64% of the variation in total hip BMD (R(2) = 0.64, P = 0.0002), 62% of total body (R(2) = 0.62, P = 0.0003), and 55% of trochanter BMD (R(2) = 0.55, P = 0.001). Subjects were then randomized to receive GH at a dose of 12.5 microg/kg per day or placebo for 12 months in a double-blind protocol. Serum androgen levels were obtained at baseline, 1, 3, 6, 9, and 12 months after initiation of GH. Androgen levels did not increase in the women receiving GH for 12 months, compared with those receiving placebo. Stimulation of androgen secretion is therefore unlikely to be a mechanism underlying the improvement in BMD, body composition, or quality of life observed with GH administration. In conclusion, androgen levels and lean body mass may be important determinants of BMD in women with hypopituitarism. It remains to be determined whether androgen replacement therapy itself or an increase in lean body mass achieved as a result of androgen administration will result in an improvement in BMD in this population.     

Bone loss in patients treated with pulses of methylprednisolone is not negligible: a short term prospective observational study

OBJECTIVE: To examine the influence of intravenous pulsed methylprednisolone (MP) on bone mass. METHODS: 38 patients (30 women) with various rheumatic disorders requiring intravenous MP pulse treatment were examined at baseline and after 6 months with dual energy x ray absorptiometry (DXA), measuring hip and lumbar spine bone mineral density (BMD). Demographic and clinical data were collected. RESULTS: Demographics showed: mean (SD) age 48.4 (16.3) years, body mass index 24.9 (5.1) kg/m(2), and median (range) disease duration 3.2 (0.1-40.0) years. During follow up patients received a mean cumulative MP dose of 3.0 (1.6) g given as 5.7 (2.0) pulses over a median period of 5.7 (2.3-33.7) months. 34/38 (89%) patients were also pulsed with cyclophosphamide, 20 (53%) were taking oral corticosteroids, and 8 (21%) were using either bisphosphonates or oestrogen. At the end of the study mean BMD was reduced by -2.2% at the femoral neck, -1.1% at the total hip, and -1.0% at the spine L2-4. In subgroups BMD increased in patients treated with bisphosphonates or oestrogen (femoral neck +1.6%, total hip +3.2%, spine L2-4 +4.5%), whereas BMD decreased at all sites in patients not treated with antirersorptive treatment, both for users (femoral neck -4.4%, total hip -2.4%, spine L2-4 -2.1%) and non-users of concomitant oral prednisolone (femoral neck -1.7%, total hip -1.9%, spine L2-4 -2.6%). CONCLUSION: Treatment with intravenous pulses of MP leads to a high rate of bone loss. Prevention of bone loss in these patients with bisphosphonates and oestrogens should be considered.     

Effect of discontinuation of estrogen,calcitriol, and the combination of both on bone density and bone markers

In a 5-yr randomized prospective study we examined the treatment effect of estrogen replacement therapy/hormone replacement therapy (ERT/HRT), calcitriol, ERT/HRT and calcitriol, or placebo for 3 yr and the effect of discontinuation of therapy for 2 more yr on bone mineral density (BMD), calciotropic hormones, markers of bone remodeling, and calcium absorption in 489 elderly women. The treatment phase of the study was double-blinded. After discontinuing therapy for 2 yr, there was rapid bone loss in all 3 treatment groups, and most of the decrease in BMD occurred in the first year. In the ERT/HRT group, spine BMD increased 5.5% in yr 3, decreased 3.2% in yr 4, and decreased 0.7% in yr 5; femoral neck BMD increased 3.7% in yr 3, decreased 2.5% in yr 4, and decreased 0.4% in yr 5; total body BMD increased 2.1% in yr 3, decreased 1.4% in yr 4, and decreased 0.6% in yr 5. In the combination group, spine BMD increased 7.1% in yr 3, decreased 4.3% in yr 4, and decreased 0.3% in yr 5; femoral neck BMD increased 4.5% in yr 3, decreased 3.0% in yr 4, and decreased 0.01% in yr 5; total body BMD increased 2.2% in yr 3, decreased 1.5% in yr 4, and decreased 0.6% in yr 5. In the calcitriol group, spine BMD increased 1.8% in yr 3, decreased 1.8% in yr 4, and showed no change in yr 5; femoral neck BMD increased 0.2% in yr 3, decreased 0.2% in yr 4, and decreased 0.6% in yr 5; total body BMD decreased 0.4% in yr 3, decreased 0.6% in yr 4, and decreased 0.4% in yr 5. Compared with placebo, all treated groups at yr 5 had significantly higher total body BMD; only the combination group had significantly higher spine BMD (3.4%; P < 0.001) and total hip BMD (2.4%; P < 0.01.) compared with the placebo group. Compared with baseline, only spine BMD in the combination group was significantly higher (2.6%; P < 0.001) at yr 5. The increase in calcium absorption and the decrease in serum PTH levels in the calcitriol groups were reversed after discontinuation of treatment, and the decrease in bone markers was reversed in the hormone-treated groups. These results suggest that discontinuation of ERT/HRT and/or calcitriol therapy in elderly women leads to a decrease in much of the BMD gained on treatment; however, in the combination group there was a statistically significant residual effect on spine BMD.     

Increased urinary N-telopeptide cross-linked type 1 collagen predicts bone loss in patients with inflammatory bowel disease

OBJECTIVE: Reduced bone mineral density (BMD) is common in patients with inflammatory bowel disease (IBD), but the factors associated with its longitudinal rate of change have not been established. We prospectively assessed the rate of change in BMD, and its association with biochemical markers of bone turnover. METHODS: Twenty-two patients with Crohn's disease and 14 ulcerative colitis patients age 37.1 +/- 11.6 yr were followed for 2 yr. Lumbar spine (L2-L4) and femoral neck BMD were measured by dual x-ray absorptiometry at baseline and 24 months. Bone-specific alkaline phosphatase, osteocalcin, urinary N-telopeptide crosslinked type 1 collagen (NTx), parathyroid hormone, and 25-hydroxyvitamin-D were determined at baseline. RESULTS: At baseline, 59% of Crohn's patients and 43% of ulcerative colitis patients were osteoporotic, with spine or femoral neck BMD T-score < -2.5. Spine BMD, and spine and femoral neck T-scores were lower and disease duration was longer in nine patients with ileal resection compared with nonoperated patients (0.84 +/- 0.15 g/cm2 vs 0.96 +/- 0.11 g/cm2, -3.0 +/- 1.5 vs -1.7 +/- 1.3, -3.2 +/- 1.5 vs -2.2 +/- 1.0, respectively; all p < 0.05). At 24 months, 13/36 (36%) and 14/36 (39%) patients experienced spinal and femoral neck bone loss, respectively, with mean annual percent BMD changes of -2.0% and -1.5%, respectively. NTx, a bone resorption marker, inversely correlated with spinal BMD rate of change (r = -0.4, p < 0.05). Using quartiles analysis, patients with the highest NTx (Q4) experienced the greatest decrease in spine BMD compared with patients with the lowest NTx (Q1). CONCLUSIONS: Spine and femoral neck bone loss continues over time in more than one-third of IBD patients. Increased NTx level predicts spinal bone loss in IBD patients.     

Influence of muscle strength and body weight and composition on regional bone mineral density in healthy women aged 60 years and over.

Although weight, lean mass, fat mass and muscular strength are often found to be intercorrelated, the respective role of each parameter in bone mineral density (BMD) remains unknown in older women. The aim of the present study was to investigate the relationship between body weight and composition and quadriceps strength on femoral neck and lumbar spine BMD in healthy postmenopausal women. The relationship between isokinetic quadriceps strength measured by Biodex and BMD measured by dual energy X-ray absorptiometry was studied in 56 women aged 60-81 (70.5 +/- 6.2) years in multiple regression models adjusted for age, body composition and menopausal treatment. Weight and age were associated with femoral neck BMD (33 and 10% of variance accounted for, respectively) and lumbar spine BMD (23 and 8% of its variance). When body weight and quadriceps strength were excluded from the model, lean mass and age were associated with femoral neck BMD (29 and 14% of variance explained, respectively) and lumbar spine BMD (28 and 11% of variance explained, respectively). When quadriceps strength was entered into the model, it was strongly associated with femoral neck BMD (30% of variance accounted for), in addition to lean mass (9%) and age (7%), whereas it was not associated with lumbar spine BMD. In conclusion, lean mass explains a great part of the strong association between body weight and femoral neck and lumbar spine BMD. Quadriceps strength explains a great part of the association between lean mass and BMD at the femoral neck site but not at the lumbar spine site. These results suggest a site-specific effect of muscular strength on bone and a potential role of the age-related decline of muscle strength in age-related bone loss in postmenopausal women.     

Bone mineral density in patients with inflammatory bowel disease: a population-based prospective two-year follow-up study

BACKGROUND: Bone loss and osteoporosis are commonly reported in inflammatory bowel disease (IBD), especially Crohn disease (CD). The aims of the present study were to evaluate changes in bone mineral density (BMD) in IBD patients during a 2-year follow-up period, and to investigate the role played by possible contributing factors in bone loss. METHODS: Sixty patients with CD and 60 with ulcerative colitis (UC) were studied initially. Fifty-five CD and 43 UC patients were re-examined after 1 year, and 50 CD and 44 UC patients after 2 years. Lumbar spine, femoral neck and total body BMD were measured by dual X-ray absorptiometry (DXA), and Z scores were obtained by comparison with age-matched and sex-matched healthy subjects. Biochemical variables were assessed at inclusion and at the 1-year follow-up visit. RESULTS: Mean BMD values were unchanged in both CD and UC patients. In patients with repeated measurements, significant differences in Z scores (delta Z score) were found for femoral neck and total body in CD and for total body in UC. Significant bone loss occurred in 11 CD (22%) and 12 UC (27%) patients. A significant increase in BMD was found in 21 CD (42%) and 20 UC (46%) patients. In CD patients the initial BMD values for lumbar spine and femoral neck were inversely correlated to BMD changes at the same sites and the change in body mass index (BMI) was positively correlated to change in the total body BMD. C-reactive protein was significantly higher in CD patients with bone loss. Biochemical markers of bone metabolism could not be used to predict BMD changes. Although it was not significant, there was a relationship between corticosteroid therapy and bone loss in CD. CONCLUSIONS: Only minor changes in BMD were observed in both CD and UC patients during a 2-year period. The multifactorial pathogenesis of bone loss in IBD makes it difficult to assess the importance of each single contributing factor. However, our results indicate that disease activity and corticosteriod therapy are involved in bone loss in CD patients.     

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.     

A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin

Transplantation of solid organs including heart, kidney, and liver is associated with rapid bone loss and increased rate of fracture; data on bone marrow transplantation recipients (BMT) are scarce. The purpose of the present study was to examine the magnitude, timing, and mechanism of bone loss following allogeneic BMT, and to study whether bone loss can be prevented by calcium with or without calcitonin. Sixty-nine patients undergoing allogeneic BMT for malignant blood diseases were enrolled into the study. Forty-four (22 women, 22 men) completed 6 months, and 36 patients 1 year follow-up. They were randomized to receive either no additional treatment (n = 22), or oral calcium 1 g twice daily for 12 months (n = 12) or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months (n = 10). Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA). Bone turnover rate was followed with markers of bone formation and resorption (serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal (PICP) and aminoterminal propeptide (PINP), serum type I collagen carboxyterminal telopeptide (ICTP)). Serum testosterone was assayed in men. Calcium with or without calcitonin had no effect on bone loss or bone markers; consequently the three study groups were combined. During the first 6 post-transplant months BMD decreased by 5.7% in the lumbar spine and by 6.9% to 8.7% in the three femoral sites (P < 0.0001 for all); no significant further decline occured between 6 and 12 months. Four out of 25 assessable patients experienced vertebral compression fractures. Markers of bone formation reduced: B-ALP by 20% at 3 weeks (P = 0.027), PICP by 40% (P < 0.0001) and PINP by 63% at 6 weeks (P < 0.0001), with a return to baseline by 6 months. The marker of bone resorption, serum ICTP was above normal throughout the whole observation period, with a peak at 6 weeks (77% above baseline, P < 0.0001). In male patients serum testosterone decreased reaching a nadir (57% below baseline) at 6 weeks (P = 0.0003). In conclusion, significant bone loss occurs after BMT. It results from imbalance between reduced bone formation and increased bone resorption; hypogonadism may be a contributing factor in men. Bone loss can not be prevented by calcium with or without calcitonin.     

Zoledronic acid prevents bone loss after allogeneic haemopoietic stem cell transplantation

Allogeneic haemopoietic stem cell transplant (alloHSCT) patients are at increased risk of osteoporosis. Zoledronic acid (ZA) is a potent i.v. bisphosphonate; however, there are few data on ZA use after alloHSCT. The aim of this study is to examine the effect of a single 4 mg ZA infusion in alloHSCT patients with either osteoporosis (T-score < -2.5) or rapid bone loss post-alloHSCT. An uncontrolled, prospective study of 12 consecutive patients receiving ZA, predominantly within the first year post-HSCT. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the spine and proximal femur pretransplant, pre-ZA and post-ZA. The median annualized percentage change in total hip BMD between the pretransplant scan and the scan immediately before ZA was -13% (range, -51 to +3.6%). After ZA treatment, the total hip BMD increased by a median of +3.3% (range, -20.4 to +14.8%) in 75% of patients. The median annualized percentage change in femoral neck BMD between the pretransplant scan and the scan immediately before ZA was -13.2% (range, -40 to +1.0%). Post-ZA, femoral neck BMD increased by a median of +1.4% (range, -22.2 to +33.6%). Only one patient continued to lose bone from the femoral neck post-ZA infusion. The median annualized percentage change in spinal BMD pretransplant was -12.5% (range, -38 to +6.9%). Post-ZA, spinal BMD decreased by a median of -2.8% (range, -27.6 to +24.4%). Four patients continued to lose bone from the spine post-ZA. ZA reduces bone loss in most patients after alloHSCT. Our data require confirmation in a larger prospective, randomized study.     

Bone loss after total hip arthroplasty

The aim of the present study is to evaluate periprosthetic bone loss and to compare it with the bone loss in other areas of the body. We also aim to shed light on the course of bone mineral density (BMD) in patients with cemented femoral prosthesis in comparison with those with uncemented ones. We analyzed the BMD using dual-energy X-ray absorptiometry (DEXA) in a consecutively recruited convenience sample of 50 patients with cemented and uncemented total hip arthroplasty (THA). BMD was measured within the first month after surgery as well as 1 year later. In ten of the patients (20%) previously undiagnosed osteoporosis was revealed. Osteoporosis was significantly more frequently detected in patients with cemented compared to those with uncemented femoral stem. We found a significant loss in BMD in the periprosthetic femoral region compared with no losses in other body regions (lumbar spine, radius, contralateral hip). The magnitude of this loss was the highest in Gruen-Zone 7 (mean 15.2% per year). We found no BMD loss difference between patients with cemented and uncemented prosthesis in the Gruen-Zone 2–7. In conclusion these periprosthetic losses may be due to local factors such as periprosthetic bone remodeling, as they contrast with the course of BMD in the lumbar spine, radius and not operated hip.     

Loss of bone density with inhaled triamcinolone in Lung Health Study II

Inhaled glucocorticosteroids (ICS) are commonly prescribed for chronic obstructive pulmonary disease. No adverse effect on bone mineral density (BMD) has been proven. In a randomized double-blind, placebo-controlled trial at seven centers in North America, we recruited 412 current smokers or recent quitters with mild to moderate chronic obstructive pulmonary disease. They used inhaled triamcinolone acetonide, 600 mcg, or placebo, twice daily. We measured femoral neck and lumbar spine BMD at baseline and after 1 and 3 years, and serum osteocalcin at baseline, 3 months, 1 year, and 3 years. After 3 years, BMD at the femoral neck decreased 1.78% more with ICS than with placebo (p < 0.001). More participants in the ICS group experienced 6% or more loss of femoral neck BMD (p = 0.002). Lumbar spine BMD increased in the placebo group by 0.98% but decreased by 0.35% in the ICS group (a difference of 1.33%, p = 0.007). Changes in osteocalcin did not correlate with changes in BMD. Fractures, lost height, or osteoporosis diagnoses were not increased among ICS users compared with placebo users. In summary, the use of inhaled triamcinolone acetonide was associated with loss of BMD at the femoral neck and lumbar spine after 3 years of treatment.