Elevation of serum urokinase plasminogen activator receptor and liver stiffness in postoperative biliary atresia

AIM To investigate serum urokinase-type plasminogen activator receptor(u PAR) and liver stiffness in biliary atresia(BA) and examine the correlation of circulating u PAR, liver stiffness, and clinical outcomes in postoperative BA children.METHODS Eighty-five post Kasai BA children and 24 control subjects were registered. Circulating u PAR was measured using enzyme-linked immunosorbent essay. Liver stiffness was analyzed using transient elastography.RESULTS BA children had significantly greater circulating u PAR andliver stiffness scores than control subjects(P 0.001). Circulating u PAR and liver stiffness were substantially higher in jaundiced BA children than non-jaundiced BA children(P 0.001). In addition, circulating u PAR was positively associated with serum aspartate aminotransferase(r = 0.507, P 0.001), alanine aminotransferase(r = 0.364, P 0.001), total bilirubin(r = 0.559, P 0.001), alkaline phosphatase(r = 0.325, P 0.001), and liver stiffness scores(r = 0.508, P 0.001).CONCLUSION Circulating u PAR and liver stiffness values were greater in BA children than healthy controls. The increased circulating u PAR was associated with liver dysfunction in BA. As a consequence, serum u PAR and liver stiffness may be used as noninvasive biomarkers indicating the progression of liver fibrosis in post Kasai BA.     

Plasma leptin concentrations in postmenopausal women with osteoporosis

Osteoporosis is less common in obese individuals with increased bone mineral density (BMD) and plasma leptin concentrations. The aim of this study was to determine the correlation between leptin levels and BMD in postmenopausal women. The study consisted of 90 postmenopausal women with a mean age of 53.45 +/- 0.87 years who visited our outpatient clinic for the evaluation of BMD. Thirty-six post-menopausal women with osteoporosis (mean age: 54.52 +/- 1.41 years and mean body mass index (BMI, kg/m2) 29.33 +/- 0.66), 30 age- and BMI-matched postmenopausal women with normal BMD, and 24 postmenopausal women (mean age: 52.79 +/- 1.48 years and mean BMI: 29.45 +/- 0.89) with osteopenic BMD were included in the study. Plasma concentrations of leptin after an overnight fast were measured by radioimmunoassay. BMD values were measured by dual-energy X-ray absorptiometry (DEXA) at the L2-L4 lumbar spine and femoral neck. The median spine BMD value in the patient group (0.67 +/- 0.08 g/cm2, mean +/- SEM) was significantly lower than that in the control group (1.02 +/- 0.25 g/cm2, mean +/- SEM) and osteopenic group (0.87 +/- 0.05 g/cm2, mean +/- SEM) (p < 0.005). The mean spine BMD value (T score -3.63 +/- 0.25, mean +/- SEM) and the mean femur neck BMD value (T score -2.55 +/- 0.18, mean +/- SEM) of the osteoporosis group were significantly lower than that in the normal BMD group (+ 0.33 +/- 0.14 and + 0.27 +/- 0.18, P < 0.001) and in the osteopenia group (-1.74 +/- 0,1 and -1.18 +/- 0.05, p < 0.005). The mean plasma leptin concentration in the osteoporotic group (17.03 +/- 1.40 ng/ml) was not significantly different from that in the normal BMD group and the osteopenia group (16.55 +/- 1.50 ng/ml; 16.16 +/- 1.60, respectively, p > 0.150). Plasma leptin concentrations were correlated with BMI in three groups (r(s) = 0.450, p = 0.025 in normal BMD group and r(s) = 0.4254, P = 0.009 in the osteoporotic group, and r(s) = 395, p = 0.015 in the osteopenia group. There was no correlation between plasma leptin concentrations and BMD values in three groups (r(s) = -0.89 in normal BMD group, r(s) = -0.124 in osteopenia group, and r(s) = -0.195 in osteoporosis group). From this study we conclude that circulating plasma leptin does not have a significant direct influence on bone mass in postmenopausal women.     

The role of quantitative ultrasound in predicting osteoporosis defined by dual X-ray absorptiometry

The aim of this study was to establish whether quantitative ultrasound (QUS) parameters could identify patients classified as osteoporotic and osteopenic on the basis of dual energy X-ray absorptiometry (DEXA). One hundred and twenty-three patients (39 male, 84 female) with osteoporosis and suspected of having osteoporosis were included in this study. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured and bone mineral densities (BMD) of the lumbar spine and left hip was measured by DEXA. Subjects were classified into three groups (normal, osteopenic and osteoporotic) on the basis of BMD T-scores measured by DEXA. QUS parameters of the osteoporotic group were significantly lower than those of osteopenic and normal groups; there was no difference in QUS parameters between the normal and osteopenic groups. Correlations of both right and left SOS and BUA with the spine and femoral neck BMD were moderate (r = 0.343-0.539, P < 0.001). There was also reasonable correlation between DEXA and QUS T-scores (r = 0.364-0.510, P < 0.001). QUS had a sensitivity of 21% and a specificity of 95% for diagnosing osteoporosis. We concluded that, although DEXA and QUS parameters were significantly correlated, QUS parameters can not predict osteopenia as defined by DEXA, and sensitivities and specificities of QUS parameters were not sufficiently high for QUS to be used as an alternative to DEXA.     

Bone density, ultrasound measurements and body composition in early ankylosing spondylitis

OBJECTIVES: In this cross-sectional study, we evaluated bone density using both dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS) techniques and examined the changes in body composition in patients with ankylosing spondylitis (AS). METHODS: Seventy-one patients were compared with seventy-one sex- and age-matched controls. Bone mineral density (BMD) was evaluated at the lumbar spine and femoral neck with a Lunar device. Total body measurements were also performed, giving BMD and bone mineral content (BMC) of the whole body, and fat and lean masses. Broadband ultrasound attenuation (BUA), speed of sound and stiffness were measured at the calcaneus using an Achilles ultrasound device. RESULTS: The patients had significantly lower lumbar spine, femoral neck and total body BMD as compared with controls (all P < 0.05). Total body BMC was also decreased in AS (P = 0.002). On the contrary, fat and lean masses did not differ between patients and controls as observed for QUS values. Mild to good correlations were found between BMD and QUS parameters (r ranging from 0.22 to 0.53; all P < or = 0.01). When applying the World Health Organization (WHO) definition for osteoporosis, we found that 46.5% of patients had lumbar spine osteopenia and/or osteoporosis, while 26.8% had femoral neck osteopenia and/or osteoporosis (controls: 23.9 and 10%; P = 0.001 and 0.08, respectively). No relationships between disease activity (as evaluated by erythrocyte sedimentation rate, serum C-reactive protein levels and BASDAI, a clinical index of disease activity) and BMD measurements were found and only femoral neck BMD correlated with disease duration (r = -0.25; P = 0.04). Finally, the presence of talalgia in AS did not influence the QUS values. CONCLUSION: These results confirm that AS patients have decreased BMD values at both the spine and femur, and also in total body measurements, reflecting a generalized bone loss. On the contrary, soft tissue composition does not seem to be influenced by the disease. QUS parameters were found to be similar between patients and controls, suggesting that the QUS method did not provide additive information to DEXA. As it is thought that QUS provides information about qualitative properties of bone, the normal results of QUS values in our patient series argue against modifications in AS bone micro-architecture.     

Osteoporosis in eating disorders: a follow-up study of patients with anorexia and bulimia nervosa.

This study prospectively investigated the course of bone mineral density (BMD) in patients with anorexia nervosa (AN) and bulimia nervosa (BN) over a 3.6-yr follow-up period. From an initial sample of 47 female patients with an eating disorder (T1), 38 (n = 24 AN; n = 14 BN) were reassessed at follow-up (T2) (participation rate, 80.1%). For nonrecovered AN patients at T2, prevalence rates of osteopenia (-1.0 SD > or = T-score > -2.5 SD) and osteoporosis (T-score < or = -2.5 SD) at the lumbar spine were 54.2 and 20.8%, respectively. Due to an annual loss of lumbar spine BMD (-3.7 +/- 4.9%) in the chronic AN patients and a slight but insignificant annual increase (0.7 +/- 1.7%) for those who recovered, the difference in BMD between both outcome groups was more pronounced at follow-up (0.93 +/- 0.13 vs. 1.14 +/- 0.13 g/cm2; P < 0.01). Nonrecovered AN patients with binge eating/purging type showed a significantly reduced BMD compared with patients with the restricting type (0.87 +/- 0.13 vs. 1.02 +/- 0.08 g/cm2; P = 0.02). Both at baseline and follow-up, AN patients had increased rates of bone resorption, as measured by urinary desoxypyridinoline, compared with a control group (n = 42) (11.4 +/- 4.4 vs. 10.4 +/- 7.8, P < 0.001, vs. 5.6 +/- 2.4 and 10.4 +/- 7.8 nM/mM creatinine, P < 0.05, respectively). The subtype of AN and body mass index were best predictors for BMD at the lumbar spine at follow-up (R2 = 0.576). With one exception, all bulimic patients had BMD and markers of bone turnover within the normal range. These results suggest that patients with chronic AN, particularly of the binge eating/purging type, are at high risk for osteoporosis and may need additional therapy to prevent bone loss.     

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.     

High prevalence and correlates of low bone mineral density in young adults with sickle cell disease

Sickle cell disease (SCD) is a prevalent genetic disorder in which sickle hemoglobin leads to tissue hypoxia and adverse effects on bone. Published studies suggest that children with SCD often have undiagnosed osteopenia or osteoporosis. Minimal data exist on the prevalence of low bone mineral density (BMD) in adults. Our objective was to describe the prevalence of osteopenia and osteoporosis in adults with SCD and to identify patient or disease characteristics associated with low BMD. We conducted a cross-sectional study of adults with SCD. Through questionnaires, we collected data about disease course and osteoporosis risk factors. Patients underwent dual X-ray absorptiometry (DXA) measurement of BMD at the hip, spine, and forearm and sampling of blood and urine for markers of bone turnover, sickle cell disease severity, and secondary causes of osteoporosis. Our main outcome measure was prevalence of osteopenia and osteoporosis as defined by WHO criteria. Of 32 adults with SCD (14 men and 18 women) with a mean age of 34 years, 72% (95% confidence interval 53-86%) had low BMD at one or more anatomic sites. Thirteen patients were classified as osteoporotic and 10 as osteopenic. The prevalence of low BMD was greatest in the lumbar spine (66% of patients). Significant correlates of decreased BMD included low BMI (P < 0.01), male sex (P = 0.02), and low serum zinc concentrations (P < 0.01). The prevalence of osteopenia and osteoporosis in young adults with SCD is extremely high. Further research is needed to address fracture risk and therapeutic interventions.     

Prevalence and risk factors of osteoporosis in patients with Parkinson’s disease

Parkinson's disease (PD) is the most common cause of disability in the elderly. It is currently recognized as a cause of secondary osteoporosis. To evaluate the prevalence of osteoporosis in PD and detect its risk factors, 52 patients with PD (36 men/16 women) and 52 controls paired for age and sex were recruited. Clinical data including demography, disease duration and disease severity were collected. All subjects had bone mineral density (BMD) measured by dual energy X-ray absorptiometry, dorsal and lumbar spine X-ray, and biological exams (osteocalcin, CTX, parathormon). The mean age of the patients was 60.0 +/- 9.25 years [30-77], and the mean disease duration was 4.9 +/- 4.5 years [0.2-17]. Nine patients (17.3%) were osteoporotic and 28 (53.8%) osteopenic. BMD at the lumbar spine and the hip was lower among patients than controls (spine: 1.031 vs. 1.175 g/cm(2); P < 0.001; hip: 0.968 vs. 1.054; P = 0.02). PD patients with low BMD presented a more severe disease and an insufficient sun exposure and calcium intake. There was a positive statistically significant correlation between patients BMD and body mass index and negative correlation with age, severity of PD, and osteocalcin levels. The prevalence of osteoporosis/osteopenia is high in PD patients and seems related to the severity of the disease, an insufficient sun exposure and calcium intake. This osteoporosis constitutes with falls the major risk factors of fracture in PD patients.     

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.     

Bone mass density in adults with sickle cell disease

Sickle cell disease (SCD) leads to many complications including osteoporosis and osteopenia. We studied the prevalence and predisposing factors of low bone mass density (BMD) in adults with SCD. In this retrospective study, dual X-ray absorptiometry bone scans were used to determine BMD in the lumbar spine, femoral neck and ultra distal radius of 103 patients (73 females, 30 males, aged 15-80 years). Chart reviews and a patient questionnaire were used to collect patient characteristics, disease course and severity, and low BMD risk factors. The 79.6% of patients (mean age 36.5 +/- 12.5 years) had an abnormal BMD, with a predilection for the lumbar spine (P = 0.001). Analysis by 3 (low BMD versus very low BMD versus normal) or by 2 groups (abnormal versus normal) showed that abnormal BMD was associated with lower body mass index (BMI) (P = 0.003), lower Hb level (P = 0.001) and higher ferritin (P = 0.003). Low BMD patients were more likely to be SS, SC or Sbeta(0)thal than Sbeta(+)thal (P = 0.022). Abnormal BMD was not related to age, sex, menarche, SCD complications, number of crises, iron overload, treatment with hydroxycarbamide or desferal, renal disease, smoking or alcohol. Patients treated with hydroxycarbamide for at least 6 months were more likely to have an abnormal BMD. In this SCD population, abnormal BMD seemed to be independent of sex, age and menopause, whereas BMI, ferritin level, Hb type and level appeared to play a major role.     

Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: a randomized controlled trial.

We conducted a randomized controlled trial in osteoporotic adult GH-deficient (GHD) patients to assess whether additional treatment with a bisphosphonate would further favorably influence parameters of bone turnover and bone mineral density measurements (BMD). All patients were receiving stable recombinant human (rhGH) replacement therapy for 4 yr at the start of the study. Eighteen GHD patients with osteoporosis were randomized to continue their rhGH maintenance dose or to receive combination therapy with rhGH and alendronate for 12 months. All patients were calcium and vitamin replete, and there were no changes in calcium, vitamin D, or hormone replacement therapy for the duration of the study. At baseline there were no significant differences between the alendronate and the control group in parameters of bone turnover, BMD, or prevalence of vertebral fractures. Childhood-onset and adult-onset GHD were equally distributed between the groups, with no statistical differences in age and gender or other parameters between groups. Mean serum osteocalcin, serum bone-specific alkaline phosphatase, and urinary N-telopeptide/creatinine ratio were within the normal range at the start of the study. In the alendronate group all measured parameters of bone turnover, i.e. bone-specific alkaline phosphatase, osteocalcin, and urinary N-telopeptide/creatinine ratio, significantly decreased after 6 months, with no further decrease thereafter. No changes were observed in the control group. In the alendronate-treated patients serum bone-specific alkaline phosphatase decreased from 10.9 +/- 0.9 to 6.8 +/- 0.7 microg/L at 6 months (P < 0.001), serum osteocalcin decreased from 3.9 +/- 0.4 to 1.7 +/- 0.3 microg/L (P < 0.001), and the urinary N-telopeptide/creatinine ratio decreased from 27.3 +/- 7.0 to 6.4 +/- 0.8 nmol/mmol (P = 0.01). In this group, lumbar spine BMD significantly increased from baseline by 3.4% at 6 months (P = 0.001) and by 4.4% at 12 months (P < 0.001) of treatment, with no further significant increase between 6 and 12 months (P = 0.217). No changes in lumbar spine BMD were observed in the control group. There were no significant changes in femoral neck BMD in either group for the duration of the study. No incident vertebral or peripheral fractures were documented in either group at the end of the study. In summary, this is the first report indicating that treatment with alendronate was able to significantly increase BMD at the lumbar spine in GHD patients with osteoporosis receiving stable rhGH replacement for 4 yr. This increase was significantly greater in alendronate-treated patients than in patients maintained on rhGH. The increase in lumbar spine BMD in the alendronate-treated patients was associated with a decrease in the measured markers of bone turnover, whereas these markers did not change further in the patients maintained on rhGH. This controlled study suggests that additional treatment with alendronate in GHD patients with osteoporosis receiving stable rhGH replacement therapy is effective in increasing BMD at the lumbar spine. Further investigation is required to assess whether rhGH replacement alone or combined treatment with rhGH and alendronate is able to reduce the increased fracture risk associated with GHD.     

The frequency of low bone mineral density and its associated risk factors in patients with inflammatory bowel diseases

Objective: To detect the frequency and the predictive factors of low bone mineral density in inflammatory bowel disease (IBD) patients, so as to optimize bone mineral density (BMD) monitoring and treatment for those at risk. Subjects and methods: Thirty Asian patients were included in this study and were divided into 18 patients with ulcerative colitis (UC), and 12 patients with Crohn’s disease (CD). All patients were diagnosed by colonoscopy and histopathological biopsy and were subjected to routine laboratory investigations in addition to 25 hydroxy vitamin D levels as well as serum calcium, phosphorus and alkaline phosphatise. BMD was measured by using dual‐energy X‐ray absorptiometry (DEXA) scan at lumbar spine and femoral neck; predictive factors for BMD were analyzed by group comparison and step‐wise regression analysis. Results: There was increased frequency of osteoporosis and osteopenia involving the lumbar spine in patients with IBD being more common among CD patients than in the UC group. Positive correlations were found between low BMD measurements and vitamin D levels, body mass index (BMI) (P < 0.001) as well as steroid cumulative dose and duration of therapy (P < 0.001); stepwise regression analysis showed that CD and vitamin D deficiency are predictive factors for both osteoporosis and osteopenia (P = 0.024, P = 0.027, respectively). Conclusion: Low BMD was found to be more frequent among patients with CD than UC; in addition CD and vitamin D deficiency act as predictive factors for low BMD. We recommend that calcium and vitamin D should be given to all IBD patients; in addition, bisphosphonate administration should be put into consideration.     

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.     

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.     

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.     

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.     

Relationship between brachial arterial endothelial function and lumbar spine bone mineral density in postmenopausal women.

BACKGROUND: Osteoporosis and endothelial dysfunction have been associated with atherosclerosis. The correlation between brachial arterial endothelial function and lumbar spine bone mineral density (BMD) in postmenopausal women will be investigated. METHODS AND RESULTS: The endothelial function in 85 postmenopausal women, including 28 women with normal spinal BMD, 27 women with osteopenia, and 30 women with osteoporosis were studied. Brachial arterial flow-mediated vasodilatation (FMD) after reactive hyperemia was assessed by ultrasonography. The BMD at the lumbar spine (lumbar 2 to 4 vertebrae) was measured by dual-energy X-ray absorptiometry. Age, years since menopause, and FMD were significantly greater in the osteoporosis group than in the normal BMD group (p<0.01, p<0.05, and p<0.05, respectively). The BMD was significantly lower in the osteoporosis group than in the osteoporosis or normal BMD group (both p<0.01). After adjusting for age and years since menopause, women with osteoporosis had significantly lesser FMD than those with normal BMD (p<0.05). The univariate linear regression analysis revealed that brachial arterial FMD was significantly positively correlated with BMD (r=0.31, p<0.01), but showed no significant association with other clinical variables. In multivariate regression analysis, the FMD was significantly positively correlated with BMD (p<0.01), but not with other variables. CONCLUSIONS: Postmenopausal women with osteoporosis might have impaired brachial arterial endothelial function, suggesting that brachial artery endothelial function might be associated with lumbar spine bone mass in postmenopausal women.     

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.     

高效抗逆转录病毒治疗对人类免疫缺陷病毒感染患者骨密度的影响

目的 评价高效抗逆转录病毒治疗(HAART)对HIV感染患者骨密度(BMD)的影响及其相关因素.方法 收集2007-2008年间50例接受HAART的HIV/MDS患者(治疗组)、12例未用HAART的HIV/AIDS患者(未治疗组)、20例健康对照者(对照组)的临床资料,采用双能X线BMD吸收仪(DEXA)测定BMD以及T值,分别对其数据进行统计分析.结果 治疗组中19例(38.0%)患者发生骨量减少,1例(2.0%)患者发生骨质疏松.对照组中5例(25.0%)发生骨量减少,无骨质疏松者.未治疗组中6例(50.0%)患者发生骨量减少,2例(16.7%)患者发生骨质疏松.未治疗组骨量减少/骨质疏松发生率较对照组显著增高(P=0.02).HIV/AIDS组(包括未治疗组和治疗组)的股骨、股骨颈、大粗隆的BMD[(0.97±0.14)、(0.91±0.13)、(0.76 4-0.12)g/cm2]明显低于对照组[(1.04±0.12)、(0.98±0.14)、(0.84±0.11)g/cm2,P<0.05];而未治疗组和治疗组的BMD差异无统计学意义.治疗组中,骨量减少/骨质疏松与体重<60 kg(r=0.074,P=0.004)、使用HAART前血浆病毒载量(r=5.103,P=0.021)呈正相关.结论 未接受HAART的HIV/AIDS患者较健康人骨量减少/骨质疏松发生率高.HIV/MDS患者BMD较健康人低,接受HAART和未接受HAART治疗的HIV/AIDS患者BMD相当.接受HAART患者中,体重<60 kg、治疗前HIV RNA是发生骨量减少/骨质疏松的危险因素.     

Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation

Osteoporosis and osteopenia affect up to half of patients with thalassaemia major (TM). We investigate the effects of acquired factors and BMT on bone mineral density (BMD) in these patients. In all, 53 patients on regular transfusion (BT group) and 33 patients at 5.7+/-1.9 years post transplant (BMT group) were recruited. BMD was measured by dual energy X-ray absorptiometry. Serum concentrations of osteocalcin, bone-specific alkaline phosphatase (ALP), beta-crossLap and urinary cross-linking deoxypyridinoline (DPD) were measured by chemiluminescence and enzyme immunoassay, respectively. Severe BMD deficit (Z-score <-2.5) at spine and hip were noted in 62 and 35% of BT group. Serum osteocalcin (beta=-0.463; P=0.006) was predictive of spine BMD, whereas age (beta=-0.843; P=0.007) and urine DPD (beta=-0.439; P=0.037) were associated with hip BMD in BT group. Among BMT patients, post transplant duration (beta=0.450; P=0.009) and serum bone-specific ALP (beta=-0.495; P=0.013) were associated with spine BMD. Severe BMD deficit was less common among BMT than BT patients (6 vs 35%; P=0.036). The mean (s.d.) osteocalcin levels in BMT and BT groups were 96.4 (72.7) microg and 68.9 (40.3) microg/l, respectively (P=0.037). In conclusion, severe BMD deficit is common in Chinese TM patients and BMT may reverse BMD deficit in these patients.