Prolactinomas in adolescents: persistent bone loss after 2 years of prolactin normalization

OBJECTIVE: To evaluate the effect of hyperprolactinaemia and its treatment with dopamine-agonists on bone mass and turnover in adolescent patients compared to adults. PATIENTS: Forty patients with hyperprolactinaemia (20 with disease onset during adolescence and 20 during adulthood) and 40 healthy control subjects. DESIGN: Open transverse (in patients and controls) and open longitudinal (in the patients). MEASUREMENTS: Bone mineral density (BMD) at lumbar spine and femoral neck, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type-1 collagen (Ntx) levels were evaluated in patients and controls. In the 40 patients, bone mass and turnover were re-evaluated after 12 and 24 months of treatment with bromocriptine (BRC, dose 2.5-10 mg daily), quinagolide (CV, dose 0.075-0.3 mg daily) or cabergoline (CAB, dose 0.5-1.5 mg weekly). RESULTS: Transverse study: BMD values were significantly lower in hyperprolactinaemic patients than in controls, both at lumbar spine (0.81 +/- 0.01 vs. 1.010 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.71 +/- 0.01 vs. 0.873 +/- 0.03 g/cm2; P < 0.001). Thirty-two patients (80%) had osteoporosis and/or osteopenia at one or both skeletal sites. A significant inverse correlation was found between T score values measured at lumbar spine and femoral neck and the estimated disease duration. BMD was significantly lower in young than adult patients both at lumbar spine (T score, -2.4 +/- 0.1 vs. -1.4 +/- 0.3, P < 0.01) and at femoral neck (T score, -2.1 +/- 0.05 vs. -1.5 +/- 0.2, P < 0.05). Similarly, serum OC levels were significantly lower (2.0 +/- 0.11 vs. 9.1 +/- 2.4 micrograms/l, P < 0. 01) while Ntx levels were significantly higher in patients than in controls (129.2 +/- 1.7 vs. 80.7 +/- 2.9 nmol Bone collagen equivalent (BCE)/mmol creatinine; P < 0.001). A significant inverse correlation was found between prolactin (PRL) levels and OC levels, lumbar and femoral T score values, as well as between disease duration and OC levels, lumbar and femoral T score values. A significant direct correlation was also found between Ntx levels and PRL levels and disease duration. Longitudinal study: Normalization of serum PRL levels was obtained in all patients after 6-12 months of treatment. A significant increase of serum OC levels together with a significant decrease of Ntx levels was observed after 12 and 24 months of treatment (P < 0.01). Urinary and serum calcium, phosphorus, creatinine, and serum alkaline phosphatase and parathyroid hormone levels did not change during the study period in all patients. After 12 months of therapy OC and Ntx concentrations were restored to normal. A slight but not significant increase of BMD values was recorded after 12 and 24 months of treatment. After 12 months of treatment the percent increment of BMD values in the whole group of patients was 1.13 +/- 0.6% at lumbar spine and 1.2 +/- 0.4% at femoral neck level, whereas after 24 months, it was 2.8 +/- 0.7% at lumbar spine and 3.5 +/- 0.7% at femoral neck level. After 12 months of treatment, the percent increment of BMD values was 0.7 +/- 0.2% and 1.6 +/- 1.1% at lumbar spine and 0.9 +/- 0.5% and 1.6 +/- 0.5% at femoral neck level in the young and adult patients, respectively, whereas after 24 months, it was 2.1 +/- 0.8% and 3.4 +/- 1.3% at lumbar spine and 2.6 +/- 0.8% and 4.4 +/- 1.0% at femoral neck level in the young and adult patients, respectively. CONCLUSIONS: Adolescents with prolactinoma have osteopenia or osteoporosis, a finding that strengthens the need for a prompt diagnosis. Since normalization of PRL concentrations by dopamine agonist therapy is unable to restore the bone mass, other therapeutic approaches should be considered in order to prevent further long-term problems.     

Frequency of osteopenia in children and young adults with childhood-onset systemic lupus erythematosus

OBJECTIVE: To determine the frequency of osteopenia in patients with childhood-onset systemic lupus erythematosus (SLE) compared with that in healthy matched controls, and to evaluate the relationship between disease-related variables and bone mineral mass. METHODS: Bone mineral density (BMD) and bone mineral content (BMC) were measured in a cohort of 70 patients with childhood-onset SLE (mean +/- SD disease duration 10.8 +/- 8.3 years, mean +/- SD age 26.4 +/- 9.9 years) and 70 age- and sex-matched healthy controls. BMD and BMC of the femoral neck, lumbar spine, total body, and distal one-third of the radius were measured by dual x-ray absorptiometry. We investigated the relationship between BMC and the following disease variables: cumulative dose of corticosteroids, organ damage, current use of corticosteroids, use of cyclophosphamide, age at disease onset, and disease activity at the time of diagnosis. Biochemical markers of bone metabolism were also measured. RESULTS: BMD values for the lumbar spine and femoral neck were significantly lower in patients than in healthy controls. The reduction in BMD of the lumbar spine was significantly greater than that of the total body. In multiple linear regression analyses, a higher cumulative corticosteroid dose was significantly associated with lower BMC of the lumbar spine and femoral neck. Decreased lumbar spine BMC was also related to male sex. CONCLUSION: The frequency of osteopenia was higher in patients with childhood-onset SLE than in matched controls. The lumbar spine was the most seriously affected skeletal site, followed by the femoral neck. The cumulative dose of corticosteroids was shown to be an important explanatory variable for BMC values in the lumbar spine and femoral neck.     

Bone mineral density in women with ankylosing spondylitis

OBJECTIVE: To determine bone mineral density (BMD) in premenopausal women with early ankylosing spondylitis (AS). METHODS: Eighteen premenopausal women with AS without syndesmophytes, interapophysiary arthritis, and/or coxofemoral joint destruction were studied. BMD was analyzed at lumbar spine and femoral neck by dual energy x-ray absorptiometry (Hologic QDR 1000). Z scores and T scores related to the general Spanish population were recorded. Comparisons were performed using the Student t test. Pearson's correlation coefficients were used to study the correlation between BMD and the variables. Following the WHO classification, osteopenia was diagnosed in patients with T score between -1 and -2.5 and osteoporosis in those with T score < -2.5 at lumbar spine or femoral neck. RESULTS: The mean Z score for spine BMD was -0.19+/-0.7, and -0.03+/-0.85 for femoral neck BMD. There were no significant differences of Z score values compared to the general population. No significant correlation was found between BMD and disease duration, radiology sacroiliac score, and spine mobility. Densitometry showed osteopenia in 2 patients and osteoporosis in none. CONCLUSION: We found a slight reduction in BMD in premenopausal women with early AS, but the difference was not statistically significant. We discuss the factors related to its pathogenesis.     

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.     

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.     

Maintenance infliximab treatment is associated with improved bone mineral density in Crohn's disease

OBJECTIVES: Diminished bone mineral density (BMD) is a recognized complication of Crohn's disease (CD). The mechanisms underlying bone loss are unclear but may include a direct effect of inflammatory cytokines related to disease activity. Because tumor necrosis factor alpha (TNF-alpha) plays a central role in the pathogenesis of CD inflammation, we evaluated the effect on BMD of maintenance treatment with infliximab in patients with CD. METHODS: BMD of the lumbar spine (L2-L4) and proximal left femur (neck and trochanter) were measured at baseline and 1 yr in 46 CD patients treated with infliximab (5 mg/kg) at 6-8 wk intervals for 1 yr. Thirteen patients received concurrent prednisone at a mean dose of 10 mg/day (range: 5-15). RESULTS: At baseline, reduced BMD (T-score 相似文献   

鲑鱼降钙素鼻喷剂治疗绝经后骨质疏松患者骨密度及骨转换指标的变化

目的 观察鼻喷鲑鱼降钙素(calcitonin)治疗绝经后骨质疏松症(postmenopausal osteoporosis,PMO)患者6个月和12个月后骨密度及骨转换指标的变化.方法 选择PMO患者共67例,给予鼻喷降钙素治疗37例;其余30例PMO患者单纯服用钙剂和维生素D作为对照组.各组分别于用药前和用药后6个月和12个月采用DEXA骨密度仪测定骨密度;定量夹心酶联免疫法(ELISA)测定Ⅰ型胶原N末端肽(NTX)、骨特异性碱性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRACP-5b)、25-羟维生素D,化学发光法测定骨钙素(BGP).结果 5例患者因医疗费用、拒绝坚持治疗退出试验,鼻喷降钙素组共32例完成试验.鼻喷降钙素治疗6个月后可见患者股骨颈和腰椎骨密度均较前有所增加,但仅在腰椎差异有统计学意义(P＜0.05),而在股骨颈治疗前后骨密度的差异无统计学意义(P＞0.05).治疗12个月时股骨颈和腰椎骨密度较前均明显升高,差异有统计学意义(P＜0.05).对照组在治疗6个月时的腰椎和治疗12个月时的股骨颈和腰椎部位骨密度均较治疗前降低,差异有统计学意义(P＜0.05).鼻喷降钙素治疗6个月和12个月时,股骨颈和腰椎骨密度均较对照组升高(P＜0.05).鼻喷降钙素治疗6个月后,TRACP-5b、NTX/Cr较治疗前降低,差异有统计学意义(P＜0.05);治疗12个月后,除TRACP-5b、NTX/Cr较前降低更加明显以外(P＜0.01),BALP较治疗前有升高,差异有统计学意义(P＜0.05).对照组在治疗12个月时,BALP较前有降低,差异有统计学意义(P＜0.05).25-羟维生素D在各组经治疗后,均明显升高,差异有统计学意义.结论 本研究结果显示鼻喷降钙素治疗6个月有效,12个月效果显著,可预防骨丢失,增加骨量.

Abstract：

Objective To study the changes of bone mineral density(BMD)and bone turnover in postmenopausal osteoporotic patients treated with salmon calcitonin nasal spray. Methods Sixty-seven postmenopausal osteoporotic patients were enrolled in our trial. All of them received calcium and vitamin D; 37patients were treated with salmon calcitonin nasal spray for 12 months and the other 30 patients received calcium and vitamin D only. Dual-energy X-ray absorptiometry(DEXA)and measurements of a series of bone turnover indices were performed before and after medication for 6 and 12 months. Results After treatment with salmon calcitonin nasal spray for6 months, BMD in lumbar spine 2-4 increased but no change occurred in femoral neck. However, after treatment for 12 months, BMD in both lumbar spine 2-4 and femoral neck increased. In the control group, BMD in lumbar spine 2-4 decreased after treatment for 6 and 12 months, but BMD in femoral neck decreased only after 12months. Comparing with the control group, after treatment with salmon calcitonin nasal spray, BMD in lumbar spine 2-4 and femoral neck were increased obviously. The level of TRACP-5b and NTX/Cr decreased after treatment with salmon calcitonin nasal spray for6 months and 12 months, while BALP increased only after treatment for 12 months. In the control group, BALP decreased after treatment for 12 months. The level of 25-(OH)vitamin D increased after treatment for 6 months and 12 months in both groups. Conclusions Long-term treatment with salmon calcitonin nasal spray prevents bone loss and may increase bone mass.     

Serum osteoprotegerin and its ligand in cirrhotic patients referred for orthotopic liver transplantation: relationship with metabolic bone disease.

AIMS: A prospective study was carried out in 22 cirrhotic patients referred for orthotopic liver transplantation, in order to analyze serum osteoprotegerin (OPG) and RANKL levels and their relationship with metabolic bone disease. METHODS: Serum levels of OPG and RANKL were measured in all patients as well as bone markers, serum parathyroid hormone and 25-hydroxyvitamin D levels. OPG and RANKL values were compared with those obtained in 29 healthy controls. Bone mineral density (BMD) of the lumbar spine and proximal femur was measured by dual X-ray absorptiometry and spinal X-rays were obtained to assess vertebral fractures. RESULTS: Serum OPG levels were higher in cirrhotic patients than in controls (6.4+/-2 vs 2.7+/-0.7 pmol/l; P=0.001) and RANKL serum levels were lower in cirrhotic patients (0.215+/-0.6 vs 1.012+/-1.2 pmol/l; P=0.002), with an increased OPG:RANKL ratio when compared with the control group (280.3+/-334.5 vs 113+/-137.6; P=0.04). Ten patients had osteoporosis (45%) and up to 45% skeletal fractures. No differences were found in OPG levels between patients with and without osteoporosis by densitometric criteria or fractures. Negative correlations were found between OPG levels and femoral neck (R-0.46; P=0.03) and total hip BMD (R-0.48; P=0.025). By contrast, OPG values were not related to markers of bone turnover. CONCLUSIONS: OPG values are elevated in cirrhotic patients before liver transplantation, particularly in those with low bone mass at the proximal femur.     

Usefulness of bone densitometry in postmenopausal women with clinically diagnosed vertebral fractures

OBJECTIVE: To analyse whether bone mineral density (BMD) assessment is required in postmenopausal women presenting with low trauma vertebral fracture. METHODS: Women with vertebral fracture diagnosed over a 10 year period were recruited from our database. The following were excluded: (a) patients with high energy trauma; (b) patients with malignancies; (c) patients with a metabolic bone disease other than osteoporosis. All postmenopausal women were included in whom BMD had been evaluated at both the lumbar spine and femoral neck by dual energy x ray absorptiometry during the six months after the diagnosis. Patients with a potential cause of osteoporosis other than age and menopause were not considered. A total of 215 patients were identified. RESULTS: The mean (SD) age of the patients was 65.9 (6.9) years. BMD at the lumbar spine was 0.725 (0.128) g/cm(2) and the T score was -2.94 (1.22); BMD at the femoral neck was 0.598 (0.095) g/cm(2) and the T score was -2.22 (0.89). The BMD of the patients was significantly lower than that of the general population at both the lumbar spine and femoral neck. When the lowest value of the two analysed zones was considered, six patients (3%) showed a normal BMD, 51 (23.5%) osteopenia, and 158 (73.5%) osteoporosis. The prevalence of osteoporosis at the femoral neck increased with age; it was 25% in patients under 60, 35% in patients aged 60-70, and 60% in patients over 70. CONCLUSION: These results indicate that bone densitometry is not required in postmenopausal women with clinically diagnosed vertebral fractures if it is performed only to confirm the existence of a low BMD.     

Effects of 42 months of GH treatment on bone mineral density and bone turnover in GH-deficient adults.

OBJECTIVE: To study the effects of GH treatment for up to 42 months on bone mineral density (BMD) and bone turnover. DESIGN AND METHODS: BMD with dual energy X-ray absorptiometry, serum type I procollagen carboxy-terminal propeptide (PICP), serum type I collagen carboxy-terminal telopeptide (ICTP) and serum IGF-I were assessed in 71 adults with GH deficiency. There were 44 men and 27 women, aged 20 to 59 (median 43) years. Thirty-two patients completed 36 months and 20 patients 42 months of treatment. RESULTS: The BMD increased for up to 30-36 months and plateaued thereafter. In the whole study group, the maximum increase of BMD was 5.0% in the lumbar spine (P<0. 001), 5.9% (P<0.01) in the femoral neck, 4.9% (NS, P>0.05) in the Ward's triangle and 8.2% (P<0.001) in the trochanter area. The serum concentrations of PICP (202.6+/-11.5 vs 116.3+/-5.4 microg/l; mean+/-s.e.m.) and ICTP (10.5+/-0.6 vs 4.4+/-0.3 microg/l) doubled (P<0.001) during the first 6 months of GH treatment but returned to baseline by the end of the study (130.0+/-10.4 and 5.6+/-0.7 microg/l respectively), despite constantly elevated serum IGF-I levels (39. 6+/-4.1 nmol/l at 42 months vs 11.9+/-0.9 nmol/l at baseline; P<0.001). The responses to GH treatment of serum IGF-I, PICP, ICTP (P<0.001 for all; ANOVA) and of the BMD in the lumbar spine (P<0.05), in the femoral neck and the trochanter (P<0.001 for both) were more marked in men than in women. At the end of the study the BMD had increased at the four measurement sites by 5.7-10.6% (P<0.01-0.001) in patients with at least osteopenia at baseline and by 0.1-5.3% (NS P<0.05) in those with normal bone status (P<0.001 for differences between groups; ANOVA). Among patients who completed 36-42 months of treatment, the number of those with at least osteopenia was reduced to more than a half. The response of BMD to GH treatment was more marked in young than in old patients at three measurement sites (P<0. 05-<0.001; ANOVA). In the multiple regression analysis the gender and the pretreatment bone mass appeared to be independent predictors of three measurement sites, whereas the age independently determined only the vertebral BMD. CONCLUSIONS: GH treatment in GH-deficient adults increased BMD for up to 30-36 months, with a plateau thereafter. Concurrently with the plateau in BMD the bone turnover rate normalized. From the skeletal point of view GH-deficient patients exhibiting osteopenia or osteoporosis should be considered as candidates for GH supplementation of at least 3-4 years.     

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.     

Bone metabolism in patients more than five years after bone marrow transplantation

We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG)--antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P=0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.     

Young adults with juvenile arthritis in remission attain normal peak bone mass at the lumbar spine and forearm

OBJECTIVE: To assess the impact of disease activity on acquired peak bone mass and bone turnover in young adult patients with either persistent juvenile arthritis (JA) or a history of JA (JA in remission). METHODS: Two hundred twenty-nine patients with JA were studied after a mean +/- SD of 15.6 +/- 2.4 years in women and 14.9 +/- 2.1 years in men since disease onset. One hundred forty-five women and 84 men were over the age of 20 at the time of examination (mean +/- SD age 24.9 +/- 2.9 years for women and 25.2 +/- 3.1 years for men). Forty-one healthy women (mean +/- SD age 27.4 +/- 3.1 years) and 55 healthy men (mean +/- SD age 25.7 +/- 3.1 years) served as a reference group. Bone mineral density (BMD) was analyzed by dual x-ray absorptiometry. Serum osteocalcin concentrations and urinary concentrations of deoxypyridium (D-Pyd) were measured. Linear regression analyses were performed to evaluate the impact of disease on BMD. RESULTS: Patients with persistent disease had significantly lower BMD compared with healthy subjects (P < 0.001 for women at all measured sites and for men at the femoral neck and total body; P < 0.05 for men at the radius and lumbar spine). Of the patients with a history of JA, only women had significantly lower BMD at the femoral neck and total body (P < 0.05). Patients with persistent JA had significantly more osteopenia and osteoporosis than healthy subjects, while patients with a history of JA had more frequent osteopenia only in the total body. Weight, urinary concentration of D-Pyd, and belonging to the patient group significantly affected BMD at all measured sites in the entire study population, while analysis of all patients found that only the number of months taking corticosteroids significantly affected BMD at all measured sites. However, the impact of the variables differed from site to site. CONCLUSION: Our findings imply that most young adults with JA attain the same BMD as healthy subjects if the disease goes into remission, while young adults with active disease have increased risk for osteopenia and osteoporosis.     

TNF-alpha gene polymorphism and plasma TNF-alpha levels are related to lumbar spine bone area in healthy female Caucasian adolescents

OBJECTIVE: The cytokine tumor necrosis factor alpha (TNF-alpha) is an important regulator of bone metabolism. Polymorphisms in the promoter region of the TNF-alpha gene at positions -308 and -863 have been identified. We investigated whether these polymorphisms and circulating TNF-alpha levels were related to bone mineral density and bone area in adolescent girls. DESIGN: Bone mineral density (BMD), bone area (BA), anthropometric characteristics and biochemical analyses were measured in adolescent girls and compared with regard to TNF-alpha genotype. METHODS: Allelic variants of the TNF-alpha gene in 97 girls, aged 16.9+/-1.2 years (mean+/-S.D.), were identified using polymerase chain reaction and the restriction endonucleases NcoI and TaiI. Bone mineral density and bone area of the femoral neck, lumbar spine and total body were measured using dual energy X-ray absorptiometry. RESULTS: Carriers of the rare -863 A allele (n=25) had higher body weight (P=0.03), lumbar spine BMD (P=0.02), and larger total BA (P=0.03), femoral neck area (P<0.05), and lumbar spine area (P=0.01). The independent predictors of BMD and BA were investigated using multiple regression. The TNF-alpha-863 genotypes (beta=0.18, P=0.03) and the TNF-alpha plasma levels (beta=0.19, P=0.04) independently predicted BA of the lumbar spine but not BA or BMD of any other measured sites. No statistically significant differences in body constitution parameters, biochemical parameters, bone density, or bone area at the measured skeletal sites were found when comparing the groups defined by the allelic variants at position -308 (P=0.17-0.84). CONCLUSIONS: We found the TNF-alpha-863 polymorphism and the TNF-alpha plasma levels to be independent predictors of lumbar spine area in healthy Caucasian adolescent females.     

Bone loss in pediatric renal transplant recipients

The factors that affect bone mineral density (BMD) and the long term progress of BMD after transplantation in children is still unknown. Therefore we performed a cross-sectional study to determine BMD in 83 recipients who received living renal allotransplants in Mansoura Urology & Nephrology Center between 1981 and 2001 (mean age at transplantation 13.2 +/- 3.1 years) by dual energy x-ray absorptiometry at various time intervals up to 16 years after transplantation (mean duration after transplantation was 48 +/- 34 months, range 6-192 months). The Z-score for lumbar spine was -2.28 +/- 2.06 and -1.44 +/- 1.44 for the total body. Osteopenia/osteoporosis were present in about two thirds of our kidney transplant recipients. The significant predictors for osteopenia/osteoporosis by univariate analysis were cyclosporine based immunosuppression, the cumulative steroid dose/m2 surface area, graft dysfunction and the urinary deoxypyridinoline. Using logistic regression analysis the cumulative steroid dose/m2 surface area and the urinary deoxypyridinoline were the major significant predictors for bone loss.     

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.     

Corticosteroid-induced osteoporosis: does it occur in patients with Crohn's disease?

OBJECTIVE: In Crohn's disease, osteoporosis is frequently found. However, the etiology of osteoporosis remains unclear. The aim of this study was to determine disease-related variables predictive for impaired bone mineral density (BMD). METHODS: A total of 91 patients with Crohn's disease who were admitted for BMD assessment were enrolled in the study. BMD was measured at the femoral neck and lumbar spine by dual energy x-ray absorptiometry (DXA). Results were expressed as T-score and as age- and sex-matched Z-score. Data were obtained by a questionnaire and from patients' medical records. Stepwise linear regression analysis was used to determine independent variables predictive for BMD. RESULTS: Mean age at BMD assessment was 41 +/- 12 yr, duration of disease 11.6 +/- 8.5 yr, and body mass index (BMI) 23.0 +/- 4.1 kg/m2. The cumulative dose of steroids used was 18.7 +/- 19.2 g. Mean Z-scores were less than zero (spine, -1.1 +/- 1.3 SD; femur, -1.1 +/- 1.2 SD; p < 0.0001). A total of 27 patients (30%) fulfilled the World Health Organization criteria for osteoporosis and 46 patients (50%) for osteopenia. Osteoporotic patients used more corticosteroids and had longer duration of disease, lower BMI, and more bowel resections than patients with normal BMD. However, in the linear regression analysis, the only significant independent predictors for BMD of the lumbar spine and femoral neck were BMI and history of bowel resections. BMI and history of resections together accounted for 28% of BMD Z-scores. CONCLUSIONS: BMI and a history of bowel resections were significant predictive variables for BMD. Despite the high dose of steroids used in this study, no detrimental effect could be demonstrated as independent predictor for osteoporosis.     

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.     

Frequency of osteopenia in children and young adults with childhood‐onset systemic lupus erythematosus

Objective

To determine the frequency of osteopenia in patients with childhood‐onset systemic lupus erythematosus (SLE) compared with that in healthy matched controls, and to evaluate the relationship between disease‐related variables and bone mineral mass.

Methods

Bone mineral density (BMD) and bone mineral content (BMC) were measured in a cohort of 70 patients with childhood‐onset SLE (mean ± SD disease duration 10.8 ± 8.3 years, mean ± SD age 26.4 ± 9.9 years) and 70 age‐ and sex‐matched healthy controls. BMD and BMC of the femoral neck, lumbar spine, total body, and distal one‐third of the radius were measured by dual x‐ray absorptiometry. We investigated the relationship between BMC and the following disease variables: cumulative dose of corticosteroids, organ damage, current use of corticosteroids, use of cyclophosphamide, age at disease onset, and disease activity at the time of diagnosis. Biochemical markers of bone metabolism were also measured.

Results

BMD values for the lumbar spine and femoral neck were significantly lower in patients than in healthy controls. The reduction in BMD of the lumbar spine was significantly greater than that of the total body. In multiple linear regression analyses, a higher cumulative corticosteroid dose was significantly associated with lower BMC of the lumbar spine and femoral neck. Decreased lumbar spine BMC was also related to male sex.

Conclusion

The frequency of osteopenia was higher in patients with childhood‐onset SLE than in matched controls. The lumbar spine was the most seriously affected skeletal site, followed by the femoral neck. The cumulative dose of corticosteroids was shown to be an important explanatory variable for BMC values in the lumbar spine and femoral neck.

     

Effect of salmon calcitonin on bone mineral density and calcium-phosphate metabolism in chronic hemodialysis patients with secondary hyperparathyroidism

The aim of the study was to evaluate the effect of salmon calcitonin on bone mineral density, parathyroid and thyroid C cells, and calcium-phosphate metabolism in chronic hemodialysis patients with uremic hyperparathyroidism. Forty five patients with serum 1-84 PTH >220 pg/ml were divided into 2 groups: group I (n = 25), treated with intranasal salmon calcitonin (200 IU, thrice a week) and control group II (n = 20). Patients received calcium carbonate (up to 6 g/d) alone or with aluminum hydroxide (up to 3 g/d) as phosphate binders; dialysate calcium was 1.75-2 mmol/l. The observation period was 12 months. The following parameters were measured: bone mineral density (BMD) with dual-energy X-ray absorptiometry in: lumbar spine (L2-L4), femoral neck and total body, before and after the study; serum endogenous calcitonin, before and after the study; serum PTH, alkaline phosphatase and total hydroxyproline, before and after 1, 3, 6, and 12 months; and serum calcium and phosphate monthly. During 12 months of the study, a substantial reduction in BMD was observed in all examined regions in group II (-2.8 +/- 2.1%; p<0.01 in L2-L4, -2.4 +/- 2.0%; p<0.01 in femoral neck, and -1.9 +/- 1.4%; p<0.01 in total body), whereas in group I a slight increase of bone mineral was noted, however insignificant. The inhibition of bone resorption was accompanied by a marked decrease in serum hydroxyproline. No changes in parathyroid activity were noted nor any decrease in serum phosphate. The treatment had no influence on serum endogenous calcitonin; initial concentrations were elevated in 47% of patients. CONCLUSION: Intranasal salmon calcitonin: 1) has no influence on bone mineralization in dialysis patients with uremic hyperparathyroidism; 2) has no significant effect on serum phosphate concentration; 3) provided adequate calcium supplementation doesn't stimulate parathyroid glands; 4) has no influence on endogenous calcitonin secretion.