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.     

Comparison of changes in bone mineral in idiopathic and secondary osteoporosis following therapy with cyclical disodium etidronate and high dose calcium supplementation

OBJECTIVE Our clinical practice has been to offer treatment with cyclical disodlum etidronate and high dose calcium supplements (1500–1600 mg/day) to ail female patients with osteoporosis who are unable or unwilling to take hormone replacement therapy (HRT), and male osteoporotics. In a retrospective study we compared the effect of this treatment on measures of bone mineral over a 12-month period in women wlth post-menopausal and secondary osteoporosis. We also assessed its effects in 10 male osteoporotics. DESIGN A retrospective analysis of 83 consecutive patients with osteoporosis who completed 12 months of treatment with disodlum etldronate and calcium and who had a dual energy X-ray absorptiometry (DEXA) scan at baseline and foilowing 12 months of therapy. PATIENTS The study Included 73 women (45 post-meno-pausal and 28 secondary osteoporotics) and 10 men with established osteoporosis as shown by spinal and femoral bone mineral densities (BMD) > 2 standard deviations (SD) below young normals, and radioiogical evidence of osteoporosis. MEASUREMENTS Each patient had routine biochemistry at baseline, an X-ray of thoracic and lumbar spine and a DEXA scan of lumbar spine (L2-L4) and femoral neck. The DEXA scan was repeated following 12 months of therapy. RESULTS There was no difference between increase in spinal BMD in the post-menopausal (5·7%) versus secondary osteoporotic group (6·7%). There was a significant increase in spinal BMD at 12 months in the 10 male osteoporotics (9·0%, P < 0·01). No overall change in femoral neck BMD was noted. CONCLUSIONS Cyclical disodium etidronate given with hlgh dose calcium supplements is equally effective in increasing spinal bone mineral density in post-menopausal and secondary osteoporosis. It also results in a significant rise In spinal bone mineral density in male osteoporotics. Whether this produces a reduction in fracture rates is unknown.     

Short-term zoledronic acid treatment increases bone mineral density and marrow clonogenic fibroblast progenitors after allogeneic stem cell transplantation

Although osteoporosis is a relatively common complication after allogeneic stem cell transplantation, the role of bisphosphonates in its management has not yet been completely established. Thirty-two patients who underwent allogeneic stem cell transplantation were prospectively evaluated for bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) after a median period of 12.2 months. Then, 15 of the patients with osteoporosis or rapidly progressing osteopenia (bone loss > 5%/yr) received three monthly doses of 4 mg zoledronic acid iv. Fifteen patients were followed up without treatment, and all 30 patients were reevaluated after 12 months for BMD and bone turnover markers. By using enriched mesenchymal stem cells in the colony-forming units fibroblast (CFU-F) assay, we evaluated the osteogenic stromal lineage. This procedure was performed in both groups of patients at study entry and after 12 months. The average BMD loss was 3.42% at LS and 3.8% at FN during a 1-yr longitudinal evaluation in 32 patients. Subsequently, BMD increased at both LS and FN (9.8 and 6.4%, respectively) in the zoledronic acid-treated cohort. Hydroxyproline excretion decreased, and serum bone-specific alkaline phosphatase increased significantly, whereas serum osteocalcin increase did not reach the limit of significance. A significant increase in CFU-F growth in vitro was induced by in vivo zoledronic acid administration. In the untreated group, no significant change was observed in bone turnover markers, LS BMD (-2.1%), FN BMD (-2.3%), and CFU-F colony number. In conclusion, short-term zoledronic acid treatment consistently improved both LS and FN BMD in transplanted patients who were at high risk for fast and/or persistent bone loss, partly by increasing the osteogenic progenitors in the stromal cell compartment.     

Femoral neck osteopenia in patients with inflammatory bowel disease

Objective: The mechanism of bone loss in patients with inflammatory bowel disease (IBD) is not completely understood. The aim of this study was to assess indices of bone turnover and bone mineral density (BMD) in the lumbar spine and femoral neck in IBD patients.
Methods: Sixty-three patients with Crohn's disease and 41 with ulcerative colitis were studied. Serum bone-specific alkaline phosphatase (B-ALP), osteocalcin, parathyroid hormone (PTH), 25 hydroxyvitamin D, interleukin-6 (IL-6), and urinary N-telopeptide cross linked type 1 collagen (NTX) were determined. BMD of the lumbar spine and femoral neck was determined by dual x-ray absorptiometry in 59 patients.
Results: In the femoral neck 42% of the patients had osteopenia (−2.5 SD < BMD T score < −1 SD) and another 41% had osteoporosis (BMD T score < −2.5). In the spine 34% of the patients had osteopenia and additional 42% had osteoporosis. BMD T scores were lower in the femoral neck compared to the spine. Reduced BMD was unrelated to gender, disease type, lifetime corticosteroid dose, but inversely correlated with disease duration ( r =−0.36 , p < 0.05 ). Serum IL-6 was higher in IBD patients compared to controls. A reduced level of osteocalcin, a marker of bone formation, was present in 7% of patients and an increase in NTX, a marker of bone resorption, in 25% of them. Osteoporotic IBD patients (spine or hip BMD T score < −2.5) had increased serum IL-6, osteocalcin and PTH level compared to nonosteoporotic patients.
Conclusions: There is a high prevalence of reduced BMD at the spine and femoral neck in IBD patients, which is more severe in the hip. Bone turnover in osteoporotic IBD patients is associated with an increase in osteocalcin, PTH and IL-6. IL-6 may play a role in the pathogenesis of bone loss in IBD.     

Relationships between muscle strength and bone mineral density of three body regions in sedentary postmenopausal women

This cross-sectional study was designed to investigate correlations between muscle strength and regional bone mineral density (BMD) in sedentary postmenopausal women. Sixty-two women who ranged in age from 41 to 76 years were investigated. Hip and trunk muscle strength was measured by isokinetic dynamometry. Grip strength of the nondominant hand was measured using a hand-held dynamometer. Bone mineral density of the lumbar spine, femur, and distal radius was measured by dual-energy X-ray absorptiometry. Only the correlation between hip abductor strength and femoral BMD was significant (P=0.009, r=0.327). There was no correlation between trunk muscle strength and lumbar vertebral BMD or between grip strength and distal radius BMD. Subjects with osteoporosis (T score <–2.5) or osteopenia T (–2.5 to –1) and normal subjects (T>–1) exhibited similar isokinetic hip and trunk muscle strength. Women with osteoporotic distal radii had significantly lower grip strength than subjects who were osteopenic or normal at this site, but the osteoporotic group was also significantly older. In conclusion, our results indicate that the isokinetic strength of hip abductors weakly correlates with femoral BMD in postmenopausal women with and without osteoporosis. Trunk muscle strength did not correlate with lumbar vertebral BMD in either of these groups. The weaker handgrip we observed in the women with osteoporotic radii may be attributed to older age.     

Relative value of the lumbar spine and hip bone mineral density and bone turnover markers in men with ankylosing spondylitis

The purpose of this study is to evaluate bone mineral density (BMD) and bone turnover markers in men with ankylosing spondylitis (AS) and to determine their relationship with clinical features and disease activity. Serum carboxi terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) levels, and BMD of lumbar spine and proximal femur were evaluated in 44 males with AS, 18–60 years of age, and compared with those of 39 age-matched healthy men. Men with AS had a significantly lower BMD at the femoral neck and total hip as compared to age-matched controls (all p < 0.01). Osteopaenia or osteoporosis was found in 59.5% AS patients at the lumbar spine and in 47.7% at the femoral neck. Mean serum levels of OC and CTX were similar in AS patients and controls. There were no significant differences in BMD and bone turnover markers when comparing subgroups stratified according to disease duration or presence of peripheral arthritis. No correlations were found between disease activity markers and BMD or OC and CTX. In a cohort of relatively young males with AS, we found a high incidence of osteopaenia and osteoporosis. Disease activity and duration did not show any significant influence on BMD or serum levels of OC and CTX.     

Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia

Osteoporosis has emerged as an important cause of morbidity in patients with thalassemia major. Studies regarding the efficacy of bisphosphonates in thalassemia-induced osteoporosis have yielded conflicting results. We performed this prospective study to evaluate the efficacy of zoledronic acid in osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg zoledronic acid intravenously every 3 months for a total of four doses. Twenty age- and sex-matched healthy blood donors served as controls. Before each infusion and 3 months after the last infusion, we determined serum levels of osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral density (BMD) of the lumbar spine was measured at baseline and after the treatment’s completion. At baseline, OPG did not differ significantly between patients and controls (p=0.2), NTX were higher in patients although not significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1 levels significantly lower in patients than in controls (p<0.001 and p<0.006, respectively). Zoledronic acid administration resulted in a significant decrease in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a significant increase in OPG and BMD (p<0.05 for both comparisons). The change in NTX, osteocalcin and IGF-1 became significant as early as 3 months after the first administration of zoledronic acid, while the change in OPG reached significance only after three infusions. Our study supports the effectiveness of bisphosphonates in the treatment of thalassemia-induced osteoporosis.     

Effects of denosumab treatment in chronic liver disease patients with osteoporosis

BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD) patients. Denosumab has been shown to increase bone mineral density(BMD) and decrease the risk of osteoporotic fracture in the general population. However, there are few reports evaluating the efficacy of denosumab in CLD patients.AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo. The study period for evaluating efficacy and safety was 12 mo. Changes from baseline in BMD at the lumbar spine, femoral neck, and total hip were evaluated at 12 mo of denosumab treatment. Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5 b(bone resorption marker), serum total procollagen type I N-terminal propeptide(bone formation maker), and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients, 138(34.1%) patients were diagnosed with osteoporosis; among these, 78 patients met the exclusion criteria and thus 60 patients were finally included in the present study. The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine, femoral neck, and total hip were +4.44%, +3.71%, and +4.03%, respectively. Denosumab significantly improved BMD, regardless of sex, patient age, and presence of liver cirrhosis. Serum tartrate-resistant acid phosphatase-5 b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P 0.001). Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P = 0.010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.CONCLUSION Denosumab treatment was safe and increased BMD, suppressed bone turnover, and improved bone quality marker levels in CLD patients with osteoporosis, irrespective of differences in baseline characteristics.     

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.     

The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin

Objective The purpose of this study was to assess the effects of alendronate and intranasal salmon calcitonin (sCT) treatments on bone mineral density and bone turnover in postmenopausal osteoporotic women with rheumatoid arthritis (RA) receiving low-dose glucocorticoids.Methods Fifty osteoporotic postmenopausal women with RA, who had been treated with low-dose corticosteroids for at least 6 months, were randomized to receive alendronate 10 mg/day or sCT 200 IU/day for a period of 24 months. All patients received calcium supplementation 1,000 mg and vitamin D 400 IU daily. Bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter was measured annually using dual-energy X-ray absorptiometry. Bone metabolism measurements included urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), and serum osteocalcin (OC).Results Over 2 years, the lumbar spine (4.34%, P <0.001), femoral neck (2.52%, P <0.05), and trochanteric (1.29%, P <0.05) BMD in the alendronate group increased significantly. The sCT treatment increased lumbar spine BMD (1.75%, P <0.05), whereas a significant bone loss occurred at the femoral neck at month 24 (–3.76%, P <0.01). A nonsignificant decrease in the trochanteric region was observed in the sCT group (–0.81%). The difference between the groups with respect to the femoral neck and trochanteric BMD was statistically significant ( P <0.001and P <0.05, respectively). The decreases in urinary DPD (–21.87%, P <0.001), serum BAP (–10.60%, P <0.01), and OC (–19.59%, P <0.05) values were statistically significant in the alendronate group, whereas nonsignificant decreases were observed in the sCT group (–5.77%, –1.96%, and –4.31%, respectively). A significant difference was found in the DPD and BAP levels between the two treatment groups in favor of the alendronate group at all time points ( P =0.001 and P <0.05, respectively).Conclusion The results of this study demonstrated that alendronate treatment produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids.     

Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn＇s disease

AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn's disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX). RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for the bone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.     

Bone assessment in elderly women: what does a low bone ultrasound result tell us about bone mineral density?

Access to dual energy X-ray absorptiometry (DXA) can prove difficult for frail or elderly patients, and bone ultrasound may offer a practical alternative. Even after adjustment for bone mineral density (BMD), ultrasound readings are able to predict hip fracture in elderly women. We consider how bone ultrasound might contribute to bone assessment in a clinical setting. DXA remains the gold standard for bone assessment, with osteoporosis defined as a BMD result more than 2.5 S.D. below the young adult mean. Using an equivalent approach we defined an osteoporotic ultrasound result as broadband ultrasound attenuation (BUA)<54 dB/MHz. In 73 women aged 29-86 (mean 65) years DXA was used to measure BMD at lumbar spine and hip, and ultrasound to measure BUA at the heel. Correlation of BUA with BMD at femoral neck (r=0.64, P<0.001), and lumbar spine (r=0.55, P<0.001) was consistent with previously reported figures for this ultrasound system. All subjects with BUA below the 54 dB/MHz threshold value were shown to have low femoral neck BMD. Women (42%) aged over 65, but only 18% of younger women had low BUA results. In women over 65 years of age measurements of BUA achieved a sensitivity of 61% and specificity of 100% in prediction of low femoral neck BMD. Although a normal BUA did not exclude an osteoporotic BMD result at hip or lumbar spine, a low BUA appeared a highly specific predictor of low BMD at these sites. Since all those women identified as having a low BUA at the heel also had low BMD results, ultrasound appeared to identify a subgroup of elderly patients at a very high risk of fracture.     

Prevalence of osteopenia in men with prolactinoma

The aim of this cross-sectional study was to analyze bone mineral density (BMD) and prevalence of osteopenia and osteoporosis in 30 men with prolactinoma, and compare them to 22 control subjects. BMD of lumbar spine and femur was evaluated by dual-energy X-ray absorptiometry. PRL, testosterone, estradiol, sexual hormone-binding globulin and free androgen and estrogen indexes (FAI and FEI, respectively) were measured in all the subjects. In patients with prolactinoma, mean values of PRL and testosterone were calculated for the 12-month period that preceded the study. The mean T-score of the four sites analyzed by bone densitometry was lower in men with prolactinoma than in controls (p-values: lumbar spine=0.015, femoral neck <0.0001, trochanter=0.037, total femur=0.036), and 55.6% of the former presented osteopenia or osteoporosis at one or more sites (p =0.035). The lumbar spine was the most seriously affected site, where 29.6% had osteopenia and 14.8% had osteoporosis. By the time of BMD determination, significant associations were found between BMD and PRL, testosterone, FAI, estradiol, FEI, and duration of hypogonadism. Considering the period of 12 months that preceded BMD evaluation, trochanter BMD was associated with mean PRL levels, while there was an association between lumbar spine BMD and mean testosterone levels. However, the multiple regression analysis showed that estradiol was the main determinant of BMD. In conclusion, men with prolactinoma have high prevalence of osteopenia and osteoporosis. Bone loss in such patients is associated with hyperprolactinemia and hypogonadism, and mainly influenced by estrogen.     

Relationship of body composition with prevalence of osteoporosis in central south Chinese postmenopausal women

Objectives To elucidate the relationship between body composition and bone mineral density (BMD) and the prevalence of osteoporosis in central south Chinese postmenopausal women. Methods A cross‐sectional study was conducted on 954 healthy central southern Chinese postmenopausal women, aged 50–82. Total body, lumbar spine and left femur BMD and total body soft tissue composition were measured by dual X‐ray absorptiometry. Results Among the study population, 578 (60·5%) subjects were without osteoporosis and 376 (39·4%) subjects were osteoporotic. The osteoporotic women were older, shorter and thinner, had an earlier age at menopause, a lower BMD and bone mineral content (BMC) of the total body and at different sites, and had lower body mass and body mass components than the women without osteoporosis. Both fat mass and lean mass were positively correlated with age at menopause, height, weight, body mass index (BMI) and BMD at all sites. Fat mass and lean mass were also inversely correlated with age and years since menopause (P < 0·05). After controlling for age, age at menopause and height, both fat mass and lean mass were positively correlated with BMD at the lumbar_1–4 spine, the femoral neck and the total hip. Fat mass was the most significant determinant of BMD at the lumbar_1–4 spine with a higher R² change and a partial R² compared with that of lean mass, while lean mass had more impact on the total hip values. Either a fat mass below 18·4 kg or a lean mass below 33·9 kg was correlated with a higher prevalence of osteoporosis at the lumbar spine or total hip. Conclusions In central south Chinese postmenopausal women, both fat mass and lean mass are correlated with BMD at the lumbar spine and hip. Fat mass was the most significant determinant of BMD at the lumbar spine, while lean mass had more impact on the total hip value. Both lower values of fat mass and lean mass are related to a higher prevalence of osteoporosis at either the lumbar spine or the total hip. Thus, it is important to maintain a reasonable body weight to balance bone health and other metabolic disorders.     

Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study

Osteoporosis is prevalent in men with an estimated one in eight men older than 50 years suffering from osteoporotic fracture, and a higher mortality rate after fracture among men compared with women. There are few approved therapies for osteoporosis in men. This observational study assesses the efficacy and safety of risedronate in the treatment of men with primary and secondary osteoporosis. A single-center, open label, randomized, prospective 1-year study was conducted in men with primary or secondary osteoporosis. Patients were randomized to risedronate (risedronate 5 mg/day plus calcium 1,000 mg/day and vitamin D 800 IU/day) or control groups (alfacalcidol 1 μg/day plus calcium 500 mg/day or vitamin D 1,000 IU/day plus calcium 800 mg/day). Bone mineral density (BMD) measurements, X-rays of the spine, a medical history and physical exam, and patient self-assessments of back pain were performed at baseline and 12 months. Blinded semi-quantitative fracture assessment was conducted by a radiologist. A total of 316 men with osteoporosis were enrolled in the trial (risedronate, n=158; control, n=158). At 1 year lumbar spine BMD increased by 4.7% in the risedronate group versus an increase of 1.0% in the control group (P<0.001). Significant increases in BMD at the total hip and femoral neck were also observed with risedronate compared with the control group. The incidence of new vertebral fracture in the risedronate group was reduced by 60% versus the control group (P=0.028). Daily treatment with risedronate for 12 months significantly increased BMD at the lumbar spine, femoral neck and total hip and significantly reduced the incidence of new vertebral fractures. This is the first prospective, randomized, controlled trial to demonstrate a significant reduction in vertebral fractures in 1 year in men with primary or secondary osteoporosis.     

Skeletal manifestations in pediatric and adult patients with Niemann Pick disease type B

Introduction

Niemann-Pick disease (NPD) due to acid sphingomyelinase deficiency is a lipid storage disease resulting from the accumulation of sphingomyelin, predominantly within cells of the monocyte-macrophage system. In contrast to other lysosomal storage disorders, skeletal involvement in NPD has not been systematically studied.

Methods

Pediatric and adult NPD-B patients underwent medical histories and physical examinations, DEXA scans to measure bone mineral content (BMC), and bone mineral density (BMD) and computed tomography scan or MRI of the abdomen for spleen volume. Z and/or T scores were calculated for the DEXA results. For the pediatric patients adjusted mean BMC (g) and BMD (g/cm²) of the lumbar spine, hip, and femoral neck was compared to control subjects. For determination of the relationship between spleen volume and lumbar spine BMD Z score, linear correlation analyses were performed.

Results

Lumbar spine Z scores for pediatric patients ranged from 0.061 to -4.879. Statistically significant decreases were observed for the adjusted mean BMC and BMD at the lumbar spine, hip, and femoral neck between the pediatric NPD-B cohort and control subjects. Most NPD-B adults were osteopenic or osteoporotic at one or more sites according the WHO classification of BMD. In NPD-B patients, the degree of splenomegaly was inversely correlated with lumbar spine BMD Z scores.

Conclusion

Skeletal involvement is a common and previously unrecognized manifestation of NPD-B. The association between splenomegaly and BMD lends further support to spleen size as an indicator of disease severity.     

Effects of alendronate combined with hormone replacement therapy on osteoporotic postmenopausal Chinese women

To evaluate the effect of alendronate combined with hormone replacement therapy (HRT) on postmenopausal osteoporotic Chinese women living in Taiwan, we treated 151 women (age range, 47-70 years; mean, 61 years) with conjugated equine estrogen (0.625 mg), medroxyprogesterone 5 mg, and elemental calcium 500 mg daily with either alendronate 10 mg (n = 79) or placebo (n = 72), and measured their bone mineral density (BMD) at the lumbar spine and hip every 6 months for 3 years. Urine N-telopeptide of type I collagen corrected by concentration of urine creatinine (NTx/Cr) and serum osteocalcin (OC) concentration was also measured at weeks 2, 4, and every 3 months from month 3 for 2 years. Significantly higher percentage increases in BMD at the lumbar spine (P < .0001, 2-way analysis of variance) throughout the 36-month treatment period were found in the alendronate plus HRT group than in the HRT-only group. However, there was no difference in BMD at the femoral neck and trochanter between these 2 groups. Treatment with alendronate plus HRT resulted in a 10.1% increase at the L-spine BMD and a 7.7% increase at the trochanter BMD at the end of the 3-year study period (P < .01, compared with baseline at both sites). A significant decline in urine NTx/Cr was observed at week 4 in the alendronate plus HRT group, whereas in the HRT-only group, a significant decline in urine NTx/Cr occurred at month 9. By the end of 24 months, urine NTx/Cr decreased by 49.7% in the alendronate plus HRT group (P = .001 compared with a 20.4% increase in the HRT group). A significant decline in serum OC level occurred at month 3 in the alendronate plus HRT group, whereas a similar decline was observed at month 6 in the HRT-only group. By the end of 24 months, serum OC decreased by 52.2% in the alendronate plus HRT group (P < .001 compared with a 1.5% increase in the HRT-only group). Subjects treated with alendronate plus HRT had a significantly greater percentage decrease in urine NTx/Cr (P = .0001) and serum OC (P = .0007) than subjects treated with HRT only throughout the 24-month treatment period by 2-way analysis of variance comparison. There was no difference in upper gastrointestinal or drug-related side effects between groups. In conclusion, our data suggest that the use of alendronate combined with HRT for 3 years was well tolerated and it significantly increased BMD at the L-spine and hip in postmenopausal Chinese women with osteoporosis. This regimen is safe and can be used in subjects who have no satisfactory response to a single agent or who have very low BMD with multiple risks. However, this study does not indicate whether HRT plus alendronate has any greater effect on BMD than alendronate alone.     

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.     

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.     

Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.