Effect of a short-term treatment with alendronate on bone density and bone markers in patients with central diabetes insipidus.

The aim of this open prospective randomized study was to evaluate the effect of a 6-month treatment with alendronate on the bone mineral density (BMD) at lumbar spine in patients with central diabetes insipidus. Eighteen patients with central diabetes insipidus and 18 sex- and age-matched healthy subjects entered this study. At study entry, all subjects underwent BMD assessment at the lumbar spine and measurement of serum osteocalcin (OC) and cross-linked N-telopeptides of type I collagen (Ntx). Thereafter, 9 of the 18 patients were randomized to receive treatment with alendronate at a dose of 10 mg, orally, once daily for 6 months (group 1), whereas the remaining 9 patients did not receive any treatment affecting bone status during this period (group 2). After 6 months, bone metabolism and bone density study were repeated in all patients. At baseline, lumbar BMD values (0.86+/-0.03 vs. 1.01+/-0.02 g/cm2; P<0.001) and serum OC levels (4.7+/-0.3 vs. 7.9+/-0.2 microg/L; P<0.001) were significantly lower, whereas urinary Ntx levels were significantly higher [72.0+/-1.9 vs. 64.6+/-1.7 nmol bone collagen equivalents (BCE)/nmol creatinine (Cr); P<0.01] in patients than in controls. After randomization, no difference in lumbar BMD, serum OC, or urinary Ntx was found between patients of group 1 and group 2. At the 6 month follow-up, no difference in serum OC levels was found compared to baseline evaluation in patients of both group 1 and group 2. By contrast, a significant decrease in urinary Ntx levels was found in patients of group 1 (70.3+/-3.0 vs. 75.4+/-2.1 nmol BCE/nmol Cr; P<0.05), but not in patients of group 2 (68.8+/-3.3 vs. 68.5+/-3.0 nmol BCE/nmol Cr; P = NS). A significant increase in lumbar BMD values was found in patients of group 1 (0.88+/-0.04 vs. 0.83+/-0.04 g/cm2; P<0.05), whereas a significant decrease in lumbar BMD values was found in patients of group 2 (0.86+/-0.05 vs. 0.89+/-0.05 g/cm2; P<0.05). Lumbar BMD increased 7.0+/-1.5% in patients of group 1 and decreased 4.2+/-1.8% in patients of group 2 (P<0.001). In conclusion, this study demonstrated that a 6-month treatment with alendronate in patients with central diabetes insipidus was effective in significantly improving BMD at the lumbar spine, which was significantly worsened in untreated patients. Therefore, alendronate treatment could be used in patients with central diabetes insipidus with documented osteopenia or osteoporosis.     

Effect of 2 years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing's disease: a prospective study

BACKGROUND: Osteoporosis is a frequent, severe and often underestimated consequence of long-term hypercortisolism, often presenting as bone fracture. OBJECTIVE: This prospective study was designed to evaluate whether the abnormalities of bone mass and turnover can be similarly reversed in adolescent and adult patients with Cushing's disease, after correction of hypercortisolism. PATIENTS AND METHODS: Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured at diagnosis and 2 years after cure of Cushing's disease (CD) in six patients with childhood-onset and nine with adulthood-onset disease. Fifteen age-, sex- and body mass index (BMI)-matched healthy subjects served as controls. RESULTS: At diagnosis, BMD Z scores at lumbar spine and OC levels were lower (2.3 +/- 0.1 vs.-0.2 +/- 0.01; P < 0.01 and 1.6 +/- 0.1 vs. 9.6 +/- 1.2; P < 0.01 respectively) while urinary Ntx levels were significantly higher (139.9 +/- 6.1 vs. 82.0 +/- 1.6; P < 0.01) in CD patients than in controls. Among CD patients, similar values of Z scores (-2.4 +/- 0.3 vs.-2.2 +/- 0.1, P = 0.4) and OC levels (1.7 +/- 0.2 vs. 1.6 +/- 0.2, P = 0.6) were observed in adolescent and adults patients, whereas urinary Ntx levels were significantly higher (159.7 +/- 7.9 vs. 125.9 +/- 3.3, P < 0.001) in the former than in the latter group. Two years after remission from hypercortisolism, OC levels (P < 0.001) and lumbar BMD Z scores (-2.2 +/- 0.3, P < 0.05; and -1.9 +/- 0.2; P < 0.01, respectively) increased significantly, while urinary Ntx levels reduced significantly (P < 0.001) in both adolescent and adult patients. However, biochemical markers and Z scores of BMD remained significantly suppressed compared to controls. CONCLUSIONS: Bone impairment in childhood- and adulthood-onset Cushing's disease patients can be partly, but not completely, reversed 2 years after normalization of cortisol levels. Longer recovery times or additive therapeutic approaches are necessary to maximize peak bone mass in children and restore bone mass in adults with Cushing's disease.     

Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism.

Reduced bone mineral density (BMD) has been reported in patients with isolated GH deficiency (GHD) or with multiple pituitary hormone deficiencies (MPHD). To investigate whether the severity of GHD was correlated with the degree of bone mass and turnover impairment, we evaluated BMD at the lumbar spine and femoral neck; circulating insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and osteocalcin levels, and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels in 101 adult hypopituitary patients and 35 sex- and age-matched healthy subjects. On the basis of the GH response to arginine plus GHRH (ARG+/-GHRH), patients were subdivided into 4 groups: group 1 included 41 patients with a GH peak below 3 microg/L (0.9 +/- 0.08 microg/L), defined as very severe GHD; group 2 included 25 patients with a GH peak between 3.1-9 microg/L (4.7 +/- 0.4 microg/L), defined as severe GHD; group 3 included 18 patients with a GH peak between 9.1-16.5 microg/L (11.0 +/- 0.3 microg/L), defined as partial GHD; and group 4 included 17 patients with a GH peak above 16.5 microg/L (28.3 +/- 4.3 microg/L), defined as non-GHD. In all 35 controls (group 5), the GH response after ARG+/-GHRH was above 16.5 microg/L (40.7 +/- 2.2 microg/L). In patients in group 1, circulating IGF-I (P < 0.001), IGFBP-3 (P < 0.05), osteocalcin (P < 0.001), and urinary Ntx levels (P < 0.001) were lower than those in group 3-5, which were not different from each other; the t score at the lumbar spine (-1.99 +/- 0.2) and that at the femoral neck (-1.86 +/- 0.3) were lower than those in groups 3 (-0.5 +/- 0.7, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), 4 (-0.5 +/- 0.2, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), and 5 (-0.5 +/- 0.2, P < 0.001 and 0.0 +/- 0.02, P < 0.001, respectively). In patients in group 2, circulating IGF-I and IGFBP-3 levels were not different from those in group 1, whereas the t scores at the lumbar spine (-1.22 +/- 0.3) and femoral neck (-0.9 +/- 0.3) were significantly higher and lower, respectively, than those in groups 1 and 5 (P < 0.05) but not those in groups 3 and 4, and serum osteocalcin and urinary Ntx levels were significant higher than those in group 1 and lower than those in groups 3-5 (P < 0.001). To evaluate the effect of isolated GHD vs. MPHD, patients were subdivided according to the number of their hormonal deficits, such as panhypopituitarism with (10 patients) or without (31 patients) diabetes insipidus, GHD with 1 or more additional pituitary deficit(s) (36 patients), isolated GHD (7 patients), 1-2 pituitary hormone deficit(s) without GHD (10 patients), and normal anterior pituitary function (7 patients). The t score at the lumbar spine and femoral neck and the biochemical parameters of bone turnover were not significantly different among the different subgroups with similar GH secretions. A significant correlation was found between the GH peak after ARG+GHRH and IGF-I, osteocalcin, urinary Ntx levels, and the t score at the lumbar spine, but not that at the femoral neck level. A significant correlation was also found between plasma IGF-I levels and the t score at the lumbar spine and femoral neck, serum osteocalcin, and urinary Ntx. Multiple correlation analysis revealed that the t score at the lumbar spine, but not that at the femoral neck, was more strongly predicted by plasma IGF-I levels (t = 3.376; P < 0.005) than by the GH peak after ARG+GHRH (t = -0.968; P = 0.338). In conclusion, a significant reduction of BMD associated with abnormalities of bone turnover parameters was found only in patients with very severe or severe GHD, whereas normal BMD values were found in non-GHD hypopituitary patients. These abnormalities were consistently present in all patients with GHD regardless of the presence of additional hormone deficits, suggesting that GHD plays a central role in the development of osteopenia in hypopituitary patients.     

Severe impairment of bone mass and turnover in Cushing's disease: comparison between childhood-onset and adulthood-onset disease

BACKGROUND: Osteoporosis is an important, frequently unrecognized consequence of hypercortisolism. OBJECTIVE: To evaluate whether the age of onset of hypercortisolism influences its effects on bone mass and turnover. SUBJECTS: 10 with childhood-onset (co) and 18 with adulthood-onset (ao) Cushing's disease (CD); 28 age-, sex- and body mass index (BMI)-matched healthy subjects served as controls. STUDY DESIGN: Open, cross-sectional controlled. MEASUREMENTS: Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC), and urinary N-telopeptides of type I collagen (Ntx) levels. RESULTS: BMD at lumbar spine was significantly lower in all CD patients than in controls (Z score, -2.3 +/- 0.1 vs. -0.2 +/- 0.01; P < 0.001). co-CD and ao-CD patients had similar values of bone mass when expressed as Z score (-2.6 +/- 0.4 vs. -2.1 +/- 0.2; P = 0.27) or as BMD (0.728 +/- 0.03 vs. 0.78 +/- 0.03 g/cm2; P = 0.25). In particular, osteoporosis was observed in 16 patients (57.1%) [eight adolescents (80%) and eight adults (44.4%)] and none of the controls; osteopenia was found in two co-CD patients (20%) and none of the healthy adolescents, 10 ao-CD patients (55.6%) and four healthy adults (14.3%) (chi2 = 7.87, P < 0.01; chi2 = 2.99, P = 0.09, respectively). In co-CD and ao-CD patients, serum OC levels were similar and significantly lower than in controls (P < 0.01); urinary Ntx levels were significantly higher than in controls (P < 0.001) and were significantly higher in co-CD than in ao-CD patients (P < 0.001). No significant correlation was found between urinary cortisol levels, serum cortisol and age and lumbar Z score values, while a significant correlation was found between Ntx levels and disease duration (r = 0.434; P = 0.021) and plasma cortisol (r = 0.440; P = 0.019). CONCLUSIONS: Cushing's disease causes bone loss and abnormalities of bone turnover both in childhood-onset and in adulthood-onset patients. A strict follow-up of bone mass and turnover is mandatory in all patients with Cushing's disease to prevent fractures later in life and specific treatment for bone loss is strongly suggested.     

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.     

The changes in circulating osteoprotegerin after hormone therapy in postmenopausal women and their relationship with oestrogen responsiveness on bone

OBJECTIVE: Oestrogen replacement reduces the increased rate of bone remodelling after the menopause. Osteoprotegerin (OPG) is a negative regulator of osteoclast-mediated bone resorption. In vitro studies have shown that oestrogen stimulates OPG production. However, the role of OPG in physiological bone remodelling and its regulation by oestrogen in vivo remain controversial. In this study, we analysed the association between changes in serum OPG levels and bone turnover status before and after hormone therapy (HT) in healthy postmenopausal women. PATIENTS AND MEASUREMENTS: Ninety-nine healthy postmenopausal women of Korean ethnicity, aged 42-64 years (52.3 +/- 4.9 years, mean +/- SD) were enrolled in our study. Serum OPG levels were assessed by a highly sensitive sandwich-type enzyme immunoassay. Serum concentrations of osteocalcin (OC) and carboxyterminal telopeptides (CTx) were determined by electrochemiluminescence immunoassays. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: Baseline levels of OPG correlated neither a the bone formation marker, serum OC, nor with a bone resorption marker, serum CTx. No significant association of baseline OPG was found with baseline BMD measured at the lumbar spine and femoral neck. Serum OPG levels measured after 3 months and 1 year of HT decreased significantly compared to baseline (P < 0.001 in both). The changes in circulating OPG at 3 months of HT correlated with the changes in both serum OC (r = 0.226, P = 0.029) and serum CTx (r = 0.214, P = 0.038) at 3 months after HT. However, there was no significant association between the changes in circulating OPG after 3 months of HT and BMD values of the lumbar spine or femoral neck after 1 year of HT. CONCLUSIONS: Our results suggest that baseline OPG levels do not reflect bone turnover status and that serial measurements of serum OPG after HT are not a useful predictor of the long-term effects of oestrogen on bone density. The decrease in serum concentrations of OPG after HT may occur to compensate for the action of oestrogen in suppressing bone resorption.     

Secondary hyperparathyroidism due to hypovitaminosis D affects bone mineral density response to alendronate in elderly women with osteoporosis: a randomized controlled trial

OBJECTIVES: To determine whether secondary hyperparathyroidism (HPTH) due to hypovitaminosis D affects bone mineral density (BMD) response to alendronate (ALN) in elderly women with osteoporosis. DESIGN: Randomized, controlled trial with 1-year follow-up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Community-dwelling women aged 60 and older with a BMD T-score below -2.5 and secondary HPTH with vitamin D insufficiency. INTERVENTION: One hundred twenty subjects were randomly assigned to receive ALN 70 mg once a week alone or ALN 70 mg once a week plus calcitriol (1,25D3) 0.5 microg daily. MEASUREMENTS: BMD measured using dual-energy x-ray absorptiometry at the lumbar spine (L1-L4), femoral neck, and total hip and serum levels of intact PTH at baseline and 12 months. RESULTS: After 1 year, BMD of the lumbar spine, femoral neck, and total hip significantly increased from baseline in both groups (P<.001). Patients allocated to ALN plus 1,25D3 demonstrated a significantly higher increase in lumbar spine BMD than those receiving ALN alone (mean percentage+/-standard deviation 6.8+/-4.6 vs 3.7+/-3.2, P<.001). Serum levels of PTH did not change significantly at 1 year in the ALN group (mean percentage, -3.7+/-27.1, P=.13) but decreased significantly in the ALN plus 1,25D3 group (-32.1+/-22.1, P<.001). At 12 months, subjects with normalized PTH independent of therapy allocation had a greater increase in lumbar spine BMD than those with persistent HPTH (6.5+/-4.6% vs 3.7+/-3.4%, P<.001). Lumbar spine BMD changes showed a significant negative correlation with PTH at 1 year (correlation coefficient (rho) =-0.399, P<.001) and a positive correlation with PTH changes (i.e., baseline value - 1 year value; rho=0.295, P=.005). CONCLUSION: Persistence of secondary HPTH reduces BMD response to ALN in older women with osteoporosis.     

Low normal TSH levels are associated with low bone mineral density in healthy postmenopausal women

OBJECTIVE: Hyperthyroidism is accompanied by low bone mass. Because the reference range of TSH levels is defined statistically, some individuals with low normal TSH levels may have mild hyperthyroidism and reduced bone mass. We therefore determined whether serum TSH levels correlate with bone mineral density (BMD). DESIGN: A cross-sectional hospital-based survey. Participants Nine hundred and fifty-nine healthy postmenopausal women. MEASUREMENTS: We measured BMD at the lumbar spine and femoral neck using dual energy X-ray absorptiometry, and serum TSH concentrations using immunoluminometry. RESULTS: BMD at the lumbar spine and femoral neck increased with TSH level (P for trend < 0.001 at both sites). Even after adjustment for age, years since menopause and body mass index, subjects with low normal TSH levels (0.5-1.1 mU/l) had significantly lower BMDs at the lumbar spine (0.863 +/- 0.009 g/cm2 vs 0.900 +/- 0.009 g/cm2, P = 0.004) and femoral neck (0.660 +/- 0.006 g/cm2 vs 0.683 +/- 0.006 g/cm2, P = 0.006) than those with high normal TSH levels (2.8-5.0 mU/l), as well as a 2.2-fold increased risk of osteoporosis (95% confidence interval: 1.2-4.0). CONCLUSION: These results suggest that low normal TSH levels may not be physiological for postmenopausal women and, during treatment of hypothyroidism, may not be adequate for avoiding osteoporosis.     

Evaluation of bone and mineral metabolism in patients recently diagnosed with leprosy

This study was conducted to evaluate patients recently diagnosed with the tuberculoid and lepromatous forms of leprosy for bone mass, bone remodeling, and hormones related to mineral control. Eleven normal control individuals (CG) and 12 patients with leprosy (LG) matched for physical characteristics were submitted to evaluation of bone mass density (BMD) and to the determination of serum levels of PTH, 25-hydroxyvitamin D [25(OH)D], testosterone, LH, FSH, osteocalcin (OC), and urinary levels of deoxypyridinoline (DPD). The T score of lumbar spine and total radius (mean +/- SD) were significantly lower in leprosy patients (L1-L4: CG = -0.7 +/- 1.5 vs LG = -1.8 +/- 1.0 SD, P < 0.04, and total radius: CG = -1.43 +/- 0.6 vs LG = -2.1 +/- 0.8 SD, P <0.02), whereas no significant differences were observed in total hip or femoral neck T score. However, at all sites, the rate of low bone mass (T score < -1.0) was higher in LG (femoral neck: CG = 18% vs LG = 50%, total hip: CG = 27% vs LG = 42%). There was a significant difference in albumin and PTH levels between groups but not in serum 25(OH)D and OC levels or urinary DPD levels. The present results indicate that bone mass loss is an early event in leprosy patients and frequently is already present at diagnosis. Its etiopathogenesis is multifactorial, and further studies are needed to determine the most efficient way to prevent fractures in this condition. The data obtained in the present study need confirmation by the evaluation of a larger sample.     

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.     

The effect of short- and long-term growth hormone treatment on bone mineral density and bone metabolism of prepubertal children with idiopathic short stature: a 3-year study

OBJECTIVE: We recently reported that children with idiopathic short stature (ISS) have decreased lumbar spine bone mineral density (BMD) that increases after 1 year of GH therapy. The aim of this study was to confirm these short-term results and to evaluate the effect of long-term GH therapy on the BMD of children with ISS. PATIENTS AND DESIGN: We treated a group of 16 short, slow-growing but otherwise healthy non-GH-deficient prepubertal children (8 girls and 8 boys) with a chronological age of 9.5 +/- 0.9 years, a bone age of 8.1 +/- 1.2 years and a height of 124.3 +/- 6.3 cm (height-SDS of -2.1 +/- 0.6) with GH at a dose of 0.1 IU/kg/day for 3 consecutive years. MEASUREMENTS: Height was determined at 3-month intervals and annual growth velocities were calculated. Bone ages and BMD were measured every 12 months by dual-energy X-ray absorptiometry, as were serum concentrations of the carboxy-terminal propeptide of type 1 collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type 1 collagen (ICPT). RESULTS: Growth velocity increased from 4.0 +/- 0.8 cm/year to 8.7 +/- 1.5 and 8.0 +/- 1.7 cm/year at 12 and 36 months of GH therapy, respectively, while height-SDS improved from -2.1 +/- 0.6 to -1.6 +/- 0.4 after 36 months of GH (P < 0.0001). Baseline lumbar spine BMD was decreased when compared to that of a control group of healthy children paired for gender, bone age and height (0.640 +/- 0.08 g/cm2vs. 0.730 +/- 0.08 g/cm2; P < 0.003). Lumbar spine BMD increased after 1 year of GH from 0.640 +/- 0.08 to 0.749 +/- 0.08 g/cm2 (P < 0.05), reaching levels similar to that of controls followed for 1 year without therapy (0.749 +/- 0.04 g/cm2vs. 0.760 +/- 0.08 g/cm2). During this period lumbar spine BMD increased 14.5% in the ISS subjects and 3.9% in the controls. Over the following 2 years of GH therapy the lumbar spine BMD of our ISS patients increased at a rate similar to that of the control population, so that after 3 years of consecutive GH therapy the lumbar spine BMD of ISS children was comparable to that of the controls (0.784 +/- 0.12 g/cm2vs. 0.785 +/- 0.09 g/cm2). Femoral neck BMD of our patients was similar to that of the controls at baseline and at 36 months. Following 1 year of GH treatment serum concentrations of PICP increased from 229.6 +/- 63.5 to 358.6 +/- 87.9 micro g/l, while levels of ICTP increased from 9.6 +/- 5.9 to 13.7 +/- 2.1 micro g/l. After 36 months of GH therapy, PICP and ICTP values had decreased to 303.3 +/- 67.2 micro g/l and 11.3 +/- 3.3 micro g/l, respectively, and were no longer significantly different from baseline. CONCLUSIONS: Children with ISS have decreased lumbar spine BMD, which normalized after 1 year of GH. Over the next 2 years of therapy lumbar spine BMD increased at a normal rate, so that after 3 consecutive years of GH the lumbar spine BMD of children with ISS was similar to that of controls. Bone turnover increased with treatment as indicated by a rise in bone formation and bone resorption markers.     

阿仑膦酸钠治疗男性骨质疏松的随访研究

目的 探讨阿仑膦酸钠治疗男性骨质疏松对骨转换标记物的影响和1年随访后骨密度变化. 方法 78例男性骨质疏松患者.年龄60～82岁,应用阿仑膦酸钠每周70 mg,治疗12个月.治疗前和治疗后3个月、12个月分别测定血骨钙素(BGP)和Ⅰ型胶原吡啶交联终肽(ICTP)和血骨特异碱性磷酸酶(BSALP).腰椎和股骨颈骨密度测定采用双能X线骨密度仪,测量部位为1～4腰椎(L1-4)后前位和左侧全髋(股骨颈、大转子、Ward's三角、股骨干). 结果 阿仑膦酸钠治疗3个月、12个月后,血ICTP、BGP和BSALP分别下降45.8%和51.6%、32.0%和37.5%、35.3%和39.9%.治疗后12个月L1-4骨密度提高11.8%,股骨颈骨密度提高11.4%.治疗后3个月、12个月血ICTP下降与L1-4骨密度提高呈正相关(r分别为0.28、0.295,P<0.05和P<0.01),与治疗后12个月股骨颈骨密度提高呈正相关(r分别为0.262、0.333,P<0.05和P<0.01);血BGP与治疗后12个月LI1-4骨密度提高呈正相关(r分别为0.322、0.401,均为P<0.01),与治疗后12个月股骨颈骨密度呈正相关(r分别为0.277,0.284,均为P<0.05);治疗后3个月、12个月血BSALP下降与治疗后12个月L1-4骨密度提高呈正相关(r分别为0.133、0.231,均为P<0.05),与治疗后12个月股骨颈骨密度提高呈正相关(r分别为0.248、0.317,均为P<0.01). 结论 骨转换标记物BGP、ICTP和BSALP早期变化可预测阿仑膦酸钠治疗男性骨质疏松患者1年后骨密度的变化.     

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.     

Growth Hormone Deficiency in Elderly Patients with Hypothalamo-Pituitary Tumors

In 18 patients with hypothalamo-pituitary diseases aged over 60 years and in 18 sex, age- and BMI-matched healthy subjects, the results of plasma IGF-I and IGF-BP3 levels and the GH response to GHRH+arginine test (GHRH+ATT) were correlated to the results of body composition, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type I collagen (Ntx) and the bone mineral density (BMD). In 10 patients and 10 controls, the GH response to ITT was also evaluated.The GH response to GHRH+ATT and ITT was markedly reduced in patients compared to controls (3.1 ± 0.7 vs. 23.2 ± 2.3 g/L, P < 0.001 and 1.1 ± 0.3 vs. 6.4 ± 0.8 g/L, P < 0.001), so all patients were classified as GHD, though no significant difference was found in plasma IGF-I and IGF-BP3 levels between the two groups. Body composition analysis revealed a significant increase of fat mass (37.4 ± 2.2 vs. 28.0 ± 1.0%, P < 0.001), a significant decrease of lean mass (62.6 ± 2.2 vs. 72.0 ± 1.0%, P < 0.001) and total body water (45.7 ± 1.5 vs. 52.5 ± 1.1%, P < 0.001) in patients compared to controls. Serum OC levels were lower (1.9 ± 0.1 vs. 4.6 ± 0.4 g/L, P < 0.001) in patients than in controls, whereas urinary Ntx levels were similar. BMD values in lumbar spine (0.81 ± 0.02 vs. 0.90 ± 0.02 g/cm²>, P < 0.01) and femoral neck (0.70 ± 0.02 vs. 0.82 ± 0.02 g/cm², P < 0.001) were significantly lower in patients than in controls. A significant inverse correlation was found between GHD duration and lumbar spine (r = –0.73, P&1t; 0.001) or femoral neck (r = –0.81, P&1t; 0.001) BMD values and a significant direct correlation was found between GH peak after GHRH+ATT and lumbar BMD (r = 0.69, p = 0.001) in GHD patients.In conclusion, GHD in patients over 60 yrs aged with a characteristic history of hypothalamus-pituitary pathology is distinct from the physiological decline in GH secretion associated with aging.     

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.     

Low bone mass in premenopausal women with depression

BACKGROUND: An increased prevalence of low bone mineral density (BMD) has been reported in patients with major depressive disorder (MDD), mostly women. METHODS: Study recruitment was conducted from July 1, 2001, to February 29, 2003. We report baseline BMD measurements in 89 premenopausal women with MDD and 44 healthy control women enrolled in a prospective study of bone turnover. The BMD was measured by dual-energy x-ray absorptiometry at the spine, hip, and forearm. Mean hourly levels of plasma 24-hour cytokines, 24-hour urinary free cortisol, and catecholamine excretion were measured in a subset of women. We defined MDD according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). RESULTS: The prevalence of low BMD, defined as a T score of less than -1, was greater in women with MDD vs controls at the femoral neck (17% vs 2%; P = .02) and total hip (15% vs 2%; P = .03) and tended to be greater at the lumbar spine (20% vs 9%; P = .14). The mean +/- SD BMD, expressed as grams per square centimeters, was lower in women with MDD at the femoral neck (0.849 +/- 0.121 vs 0.866 +/- 0.094; P = .05) and at the lumbar spine (1.024 +/- 0.117 vs 1.043 +/- 0.092; P = .05) and tended to be lower at the radius (0.696 +/- 0.049 vs 0.710 +/- 0.055; P = .07). Women with MDD had increased mean levels of 24-hour proinflammatory cytokines and decreased levels of anti-inflammatory cytokines. CONCLUSIONS: Low BMD is more prevalent in premenopausal women with MDD. The BMD deficits are of clinical significance and comparable in magnitude to those resulting from established risk factors for osteoporosis, such as smoking and reduced calcium intake. The possible contribution of immune or inflammatory imbalance to low BMD in premenopausal women with MDD remains to be clarified.     

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.     

Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.     

A therapeutic dilemma: suppressive doses of thyroxine significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid carcinoma

We measured lumbar spine, femoral neck, and forearm bone mineral (BMD) in 24 women (14 premenopausal and 10 postmenopausal) who had been treated with total thyroidectomy and 131 Iodine ablation therapy for nonanaplastic thyroid carcinoma and 24 case controls. At the time of the study, all patients were free of cancer (negative 131 Iodine whole body scan and serum thyroglobulin levels less than 0.3 micrograms/L) and all were receiving doses of T4 sufficiently high to prevent a rise in a serum thyroid-stimulating hormone concentration after an iv bolus of TRH. Femoral neck BMD were significantly reduced in both the premenopausal women (89 +/- 3.8% of case controls, 95% CI, 81 to 98) and postmenopausal women (77 +/- 3.9% of case controls; 95% CI, 68 to 86) receiving T4. Lumbar spine BMD and forearm BMD were unaffected in the premenopausal women, but significantly reduced in the postmenopausal women receiving T4 (lumbar spine BMD = 84 +/- 6.2% of case controls; 95% CI, 70 to 98 and forearm BMD = 89 +/- 5.6% of case controls; 95% CI, 76 to 101). Serum bone Gla-protein, a marker of bone turnover, was significantly increased in both the premenopausal and the postmenopausal women receiving T4 compared to case controls (P less than 0.001 for the difference between patient groups and controls). Whereas the cumulative dose of T4 was highly correlated with the femoral neck BMD in the premenopausal patients (r = 0.528; P less than 0.05); the presence of hypogonadism was the main determinant of the lumbar spine and forearm BMD. This data confirms that premenopausal and postmenopausal women receiving suppressive doses of T4 for thyroid carcinoma have diminished bone mineral measurements and are at risk for osteoporosis.