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.     

Improvements in the management of rheumatic patients from vertebral image obtained through dual-energy X-ray absorptiometry

The diagnosis of asymptomatic vertebral fracture is clinically useful and the identification of new fractures may influences the choice of appropriate therapeutic measures. In order to identify moderate and asymptomatic vertebral deformities in an objective and reproducible manner, vertebral morphometry is performed. This method measures the vertebral body's anterior, middle and posterior heights at the dorsal and lumbar level. Currently this technique is performed on lateral images of the spine obtained through the traditional X-ray method (radiological morphometry or morphometric X-ray radiography, MRX) and, more recently from images obtained through dual-energy X-ray absorptiometry (DXA) machines (visual assessment of X-ray absorptiometry scans or morphometric X-ray absorptiometry, MXA), commonly used to measure bone mineral density. The main advantage of MXA relative to MRX is the lower radiation dose to which the patient is exposed during the exam. In addition, MXA scans offers the advantage of acquiring a single image of thoracic and lumbar spine, without any distortion (e.g.: coning). The most obvious advantage of MXA is the opportunity of obtaining during the same session a bone mineral density evaluation, and digital images that are easily processable, manageable, recordable and comparable for the patient's follow up. A limitation of the MXA technique is the inferior quality of the images, that make often impossible the detection of the vertebral edges, and the impossibility to visualize the upper thoracic vertebral bodies. MXA, despite its intrinsic limitations, when carried out by trained personnel may provide substantial improvements in the management (diagnosis and follow-up) of rheumatic patients.     

Bone metabolism and mass in women with Cushing's syndrome and adrenal incidentaloma

OBJECTIVE: The aim of this study was to compare bone turnover and mass in women with either Cushing's syndrome (CS) or adrenal incidentaloma (AI), which is a possible model for minimal hypersecretion of cortisol. DESIGN AND PATIENTS: We studied 15 patients with CS (seven premenopausal and eight postmenopausal women); 23 patients with AI (five premenopausal and 18 postmenopausal women) and 20 matched controls (seven premenopausal and 13 postmenopausal women). Alkaline phosphatase (ALP), bone alkaline phosphatase (bALP), osteocalcin (BGP), 24-h urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) and serum and 24-h urinary calcium and phosphorus were determined in all subjects. Bone mineral density (BMD) at lumbar spine and proximal femur was measured by dual energy X-ray absorptiometry (DEXA). RESULTS: We found a significant reduction of BGP and serum phosphorus in CS and AI (P < 0.05) vs. controls and significantly lower levels of Pyr only in CS (P < 0.05) vs. AI and controls. Spinal and femoral BMD z-values were significantly lower (P < 0.05) in patients with CS (z-score: lumbar spine -1.44 +/- 1.5 and femoral neck -1.07 +/- 1; mean +/- SD) compared to AI and controls. CONCLUSIONS: Our data show that hypercortisolism reduces osteoblastic function and bone resorption and that osteocalcin can contribute to the precocious diagnosis of silent glucocorticoid excess. Patients with active CS were found to have lower BMD, particularly at vertebral level.     

Clinical evaluation of spine morphometric X-ray absorptiometry

A new method for vertebral height measurements, morphometric X-ray absorptiometry (MXA) based on dual-energy X-ray absorptiometry, has been proposed. This technique overcomes some limitations of morphometric radiography (MRX): the effective radiation dose is low, some sources of geometric distortion are eliminated, such as dependence on patient position, magnification gradient, and the effect of scoliosis is minimized. The purpose of this study was to compare morphometric parameters obtained by both methods (MXA and MRX), and to evaluate the agreement between morphometric evaluations and qualitative reading for vertebral fracture diagnosis. The evaluation was performed with an Hologic QDR 2000 device in 67 women without vertebral fractures and 31 women with vertebral fractures (according to a qualitative assessment). The reproducibility of the image analysis was <4% and comparable to MRX. The estimated bias between the two methods was on average 10 mm, and was a function of the vertebral height, according to the Bland and Altman method. The agreement between MXA and other methods for vertebral fracture diagnosis was poor for the thoracic level above T7, due to a lack of resolution and rib interposition. Agreement was also low for T10, due to the motion of the diaphragm muscle. MXA cannot currently be used for the diagnosis of thoracic vertebral fracture in clinical practice. Technological improvements are necessary to make this promising method useful as a screening tool to evaluate the presence of thoracic vertebral fractures.      

Comparing morphometric X-ray absorptiometry and radiography in defining vertebral wedge fractures in patients with ankylosing spondylitis

OBJECTIVE: To compare the level of agreement of quantitative morphometry of the vertebrae on lateral views of the spine using conventional X-ray and using a dual X-ray absorptiometry device (DXA) in determining the degree of wedging of vertebrae in patients with ankylosing spondylitis (AS). METHODS: Thirty patients with AS underwent DXA to acquire single-energy morphometric X-ray absorptiometry (MXA) scans and conventional lateral radiography (MRX) of the thoracic and lumbar spine. Vertebral anterior and posterior heights were measured and the anterior/posterior (AP)-ratio was calculated. We analysed the level of agreement for vertebral wedging between MRX and MXA on the patient level and on the vertebral level, using average AP-ratios per patient, and per vertebra, as well as dichotomized AP-ratios (above or below cut-off levels that are commonly used to identify fractures). RESULTS: Per-patient analysis showed good agreement between both methods in the whole spine [intraclass correlation coefficient (ICC) = 0.64], as well as in the thoracic (ICC = 0.66) and lumbar spine (ICC = 0.62) separately. Analysis on individual vertebrae showed differences in agreement dependent on which part of the spine was measured. The ICC on all vertebrae was 0.71, 0.76 in the lumbar and 0.43 in the thoracic vertebrae. If AP-ratios were translated into fractures (yes vs no) using different cut off levels for a fracture (AP-ratios 0.75, 0.80 or 0.85) between-method agreement became fair to good (kappa 0.26-0.35 in the thoracic and 0.47-0.80 in the lumbar vertebrae). Differences in classifications were in both directions and in all vertebral fractures according to the Genant definition. In this study with a prevalence of 5% of vertebral fractures, the positive predicted value (PPV) was 39% and the negative predicted value (NPV) was 97%. CONCLUSION: Although the agreement between MRX and MXA in measuring global vertebral wedging, expressed as (mean) AP-ratio, was good, the reliability of both measures to assess wedging at the vertebral level was highly variable, ranging from fair to very good agreement, dependent on the level. If fracture studies are performed with either of both the methods, the results of wedging at the individual vertebral level cannot be generalized to the other method, except for wedging <0.75 at the lumbar spine. However, as the NPV was high, DXA could be of clinical value to select patients for further evaluation by X-ray to assess vertebral fractures as a sign of bone failure.     

Normal bone mineral density following cure of Cushing''s syndrome

OBJECTIVE: Both endogenous and exogenous glucocorticoid excess are well established as causes of osteoporosis. However, there are few data describing bone mineral density in these subjects following the restoration of normal steroid levels. The present study addresses this issue. DESIGN: A cross-sectional assessment of bone mineral density in patients cured of Cushing's syndrome, and comparison of each with four normal subjects matched by age, sex, weight, menopausal status and race, was used. PATIENTS: Seventeen adults cured of Cushing's syndrome 8.6 +/- 1.6 years (mean +/- SEM) took part. MEASUREMENTS: The bone mineral density of the lumbar spine and proximal femur was measured by dual energy X-ray absorptiometry. RESULTS: Bone mineral densities, relative to control, were 100 +/- 16, 98 +/- 14, 97 +/- 19 and 98 +/- 16% (mean +/- SD), in the lumbar spine, femoral neck, Ward's triangle and trochanteric regions, respectively. There was a positive relationship between bone density and time since cure (r = 0.24-0.59, in the four regions). In contrast, bone density was significantly reduced in five subjects with active Cushing's disease when similarly matched (BMD = 87 +/- 4, 83 +/- 4, 75 +/- 6 and 82 +/- 6%, in the respective regions; 0.01 less than P less than 0.05). CONCLUSIONS: Bone density is reduced in subjects with Cushing's syndrome but not in those having undergone cure some years previously. This implies that steroid-induced osteoporosis is substantially reversible, though long-term prospective studies will be necessary to establish this definitively.     

Bone size and volumetric density in women with anorexia nervosa receiving estrogen replacement therapy and in women recovered from anorexia nervosa

Anorexia nervosa is associated with bone loss during adulthood, but may also delay skeletal growth and mineral accrual during growth. We asked the following questions. 1) Is anorexia nervosa associated with reduced bone size and reduced volumetric bone mineral density (vBMD)? 2) Is estrogen replacement therapy (ERT) or recovery from anorexia nervosa associated with normal bone size and vBMD? Using dual-energy x-ray absorptiometry, we measured bone size and vBMD of the third lumbar vertebra and femoral neck in a cross-sectional study of 161 female patients: 77 with untreated anorexia nervosa, 58 with anorexia nervosa receiving ERT, 26 recovered from anorexia nervosa, and 205 healthy age-matched controls. Results were expressed as the SD or z-score (mean +/- SEM). Deficits in vertebral body and femoral neck width in untreated women were -1.0 +/- 0.1 and -0.3 +/- 0.1 SD (P < 0.001 and P < 0.05, respectively). Deficits in bone width were less in the ERT-treated women than in untreated women at the vertebral body (-0.6 +/- 0.1 SD; P < 0.001), but not at the femoral neck (-0.4 +/- 0.2 SD; P < 0.05). There were no significant deficits in vertebral body and femoral neck width in recovered women (both -0.3 +/- 0.2 SD; P = NS). In untreated women, vertebral and femoral neck vBMD were -1.6 +/- 0.1 and -1.1 +/- 0.1 SD, respectively (both P < 0.001), less severely reduced in ERT-treated women (-1.2 +/- 0.2 and -0.6 +/- 0.2 SD, respectively; both P < 0.001), and least reduced in recovered women (-0.6 +/- 0.1 and -0.5 +/- 0.2 SD; P < 0.01 and P < 0.05, respectively). After adjusting for differences in fat and lean mass, vertebral body and femoral neck width were no longer reduced in untreated, ERT-treated, and recovered women. Adjustment for body composition had little effect on group difference in vBMD. Bone fragility in anorexia nervosa is due to reduced bone size and reduced vBMD. Although causality cannot be inferred in cross-sectional studies, the data are consistent with the view that malnutrition may contribute to reduced bone size, whereas estrogen deficiency may reduce vBMD. The use of ERT early in disease is a reasonable component of management if the chance of recovery appears remote.     

The contribution of IGF-I to skeletal integrity in postmenopausal women

OBJECTIVES: The pathogenic role of the decline in serum concentrations of IGF-I in postmenopausal osteoporosis is not fully elucidated. We investigated the associations among IGF-I, bone mineral density (BMD), ultrasound parameters and prevalence of vertebral fractures in postmenopausal women. DESIGN: A cross-sectional study. PATIENTS: One hundred and fifty-four ambulatory postmenopausal women (61 +/- 7 years) referred for osteoporosis screening. MEASUREMENTS: IGF-I was measured by radioimmunoassay and BMD using dual-energy X-ray absorptiometry. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at calcaneus were measured by a quantitative ultrasound system. RESULTS: IGF-I was significantly lower in osteoporotic subjects and correlated positively with BMD, BUA and SOS. After adjusting for age, years since menopause and body mass index, IGF-I accounted for 8.5% of the variance at lumbar spine BMD, 4.6% at femoral neck and 7.1% at calcaneal BUA. BUA was associated with IGF-I independently of BMD. IGF-I was lower in women with vertebral fractures (91 +/- 39 microg/l vs. 114 +/- 44 microg/l; P = 0.003). The osteoporosis densitometric criteria (t-score < or = -2.5 SD) was the most strongly independent associated variable with prevalent vertebral fractures [odds ratio (OR): 3.3 (1.4-7.6)], followed by IGF-I levels below 75th percentile [OR: 3 (1-8.8)]. CONCLUSIONS: Our study shows that IGF-I is strongly associated with bone mineral density and reflects aspects of bone quality. The contribution of IGF-I to skeletal integrity in postmenopausal women is clinically relevant.     

Relationship between bone mineral density changes and fracture risk reduction in patients treated with strontium ranelate

OBJECTIVE: Our objective was to analyze the relationship between bone mineral density (BMD) changes and fracture incidence during 3-yr treatment with strontium ranelate. PATIENTS: Women from the strontium ranelate arm of the Spinal Osteoporosis Therapeutic Intervention study and the TReatment Of Peripheral OSteoporosis study were evaluated. OUTCOME MEASURES: The outcome measures included BMD at the lumbar spine, femoral neck, and total proximal femur assessed at baseline and after a follow-up of 1 and 3 yr; semiquantitative visual assessment of vertebral fractures; and nonvertebral fractures based on written documentation. RESULTS: After 3 yr of strontium ranelate treatment, each percentage point increase in femoral neck and total proximal femur BMD was associated with a 3% (95% adjusted confidence interval, 1-5%) and 2% (1-4%) reduction in risk of a new vertebral fracture, respectively. The 3-yr changes in femoral neck and total proximal femur BMD explained 76% and 74%, respectively, of the reduction in vertebral fractures observed during the treatment. Three-year changes in spine BMD were not statistically associated with the incidence of new vertebral fracture (P = 0.10). No significant associations were found between 3-yr changes in BMD and incidence of new nonvertebral fractures, but a trend was found for femoral neck BMD (P = 0.09) and for total proximal femur BMD (P = 0.07). An increase in femoral neck BMD after 1 yr was significantly associated with the reduction in incidence of new vertebral fractures observed after 3 yr (P = 0.04). CONCLUSION: During 3-yr strontium ranelate treatment, an increase in femoral neck BMD was associated with a proportional reduction in vertebral fracture incidence.     

Bilateral fractured neck of the femur in an adult patient with cystic fibrosis

A 34-year-old man with cystic fibrosis (CF) sustained a bilateral fractured neck of the femur during the course of six grand mal seizures. The fractures were successfully treated with bipolar hemi-arthroplasties. Several risk factors for osteoporosis were present. Bone pathology showed reduced femoral head bone density. Osteoporosis of the lumbar spine was confirmed by dual-energy X-ray absorptiometry. As the life expectancy of patients with CF continues to improve, osteoporosis and its sequelae will become more common. We should be aware of the increased risk of bilateral fractured neck of the femur following epileptic seizure in CF.     

绝经后妇女脊椎压缩性骨折与骨密度的关系

目的探讨绝经后妇女脊椎压缩性骨折与骨密度（BMD）的关系。方法为病例一对照研究，入选250例有脊椎压缩性骨折的绝经后妇女，另有250名无脊椎压缩性骨折的绝经后妇女作为对照组。两组均有胸腰椎正侧位X线摄片，并应用双能X线吸收仪检测腰椎1～4和左股骨近端各部位BMD。结果脊椎压缩性骨折组身高、体重、腰椎2～4和股骨近端各部位BMD值均显著低于对照组（均P〈0．01）。腰椎2～4BMD是发生脊柱骨折的预报因子（r=-0．416，P〈0．01）。身高和全髋部BMD与骨折次数和骨折椎体数目呈负相关（均P〈0．01）。按股骨颈和全髋部BMD值，骨折组骨质疏松检出率各为50．8％和50．4％；另外剔除在腰椎2～4发生椎体骨折53例，按腰椎2～4BMD检出骨质疏松占64．5％。同时，腰椎2～4、股骨颈或全髋部BMD值低于-2．5s者发生脊柱压缩性骨折的风险分别是BMD正常者的4．76、2．36和3．52倍。结论腰椎呈低骨量是发生脊椎压缩性骨折的重要危险因素。身高的下降和全髋部低BMD值是骨折发生次数和受累椎体数目的危险因子；对绝经后妇女在重视BMD测量的同时，应重视脊柱X线正侧位检查。     

The prevalence of vertebral fractures in mild ankylosing spondylitis and their relationship to bone mineral density

OBJECTIVE: To determine bone mineral density (BMD) in patients with mild ankylosing spondylitis (AS), to establish the prevalence of vertebral fractures and fracture risk in these patients, and to determine the relationship between BMD and vertebral fractures. METHODS: Sixty-six men with mild AS were studied. BMD of the lumbar spine and femoral neck was measured by dual X-ray absorptiometry (DXA) and radiographs of the thoracic and lumbar spine were obtained in all subjects. From the radiographs, vertebral fractures were characterized by a morphometric technique using established criteria. Thirty-nine healthy male subjects aged 50-60 yr, recruited from primary care registers, had spinal radiographs performed and served as controls for vertebral fractures. RESULTS: In patients with AS, BMD was reduced in both the lumbar spine 0.97 (0.1) g/cm(2) [T score -1.10 (1.3), 95% confidence interval (CI) -0.50, +0.14] and femoral neck 0.82 (0.1) g/cm(2) [T score -1.40 (1.2), 95% CI -0.51, +0.09]. There was no correlation between BMD of either the lumbar spine or femoral neck and duration of disease in patients with AS. Eleven of 66 (16.7%) patients with AS had a vertebral fracture, compared with one of 39 (2.6%) controls; odds ratio 5.92 (95% CI 1.4, 23.8). AS patients with fractures were not significantly older (mean age 41.4 vs 37.8 yr, P=0.17), but had significantly longer disease duration (12.4 vs 9.3 yr, P<0.05) than patients without fractures. No significant difference was found in the visual analogue scores for pain in AS patients with fractures compared with those without. No significant correlation was observed between BMD of the lumbar spine or femoral neck and vertebral fractures in patients with AS. In addition, there was no significant difference in the lumbar spine or femoral neck BMD in AS patients with fractures compared with those without. CONCLUSIONS: Spinal and hip osteopenia and vertebral fractures are a feature of mild AS. However, there was no correlation between BMD and vertebral fractures in these patients. AS patients with mild disease had a higher risk of fractures compared with the normal population and this increased with the duration of disease.     

Stress fractures in rheumatological practice: clinical significance and localizations

The objective of this study was to analyze the clinical characteristics, associated disorders, and the most common sites of stress fractures in rheumatological patients. Over a 3-year period, 35 patients with 44 stress fractures were prospectively recruited from an outpatient rheumatological department (32 postmenopausal women and three men aged 47 to 86 years, mean 70+/-10.6 years). Clinical diagnosis was established by compatible clinical and radiological data. In addition, previous skeletal fractures were recorded in all patients. Bone mass assessment was performed in 23 patients and spinal X-ray in 21. The diagnosis of osteoporosis was defined by the presence of atraumatic vertebral fractures and/or densitometric criteria (lumbar or femoral bone mass <-2.5 T score). The most frequent stress fractures were: pelvic ring (13 sacrum and eight pubic) and metatarsal (11 fractures), followed by tibia (seven fractures), calcaneus (three fractures), femur (one), and tarsal (one). Nine patients (26%) presented simultaneous stress fractures. Twenty-four patients (69%) suffered previous osteoporotic fractures, vertebral and Colles' fractures being the most frequent. Most of the evaluated patients (25 out of 30) had osteoporosis (83%). Six patients had associated disorders (glucocorticoids use in three patients, neurologic disorders in two, and rheumatoid arthritis in one). Except for the patient with a femur fracture which required internal fixation, no other clinical complications were observed after conservative treatment. In conclusion, fractures of the pelvic ring, especially sacrum, and metatarsal are the most frequent stress fractures in rheumatological practice. The association with osteoporosis and the history of prior low-trauma fractures are common in these patients.     

Clinical characteristics and etiologic factors of premenopausal osteoporosis in a group of Spanish women

OBJECTIVES: To analyze the clinical characteristics and the principal causes of osteoporosis in premenopausal women. METHODS: This study included 52 osteoporotic premenopausal women ages 20-51 years (mean 36.2 +/- 7) who were referred to an outpatient rheumatology department for osteoporosis evaluation. Bone mass assessment, automated biochemical profile, urinary calcium excretion, and bone marker assays were performed on all patients. Hormonal measurements were made when a specific etiology was not readily apparent. The diagnosis of osteoporosis was defined by the presence of atraumatic vertebral fractures and/or by densitometric criteria. Previous skeletal fractures, weight, height, body mass index (BMI), age at menarche, and family history of osteoporosis also were recorded. RESULTS: Twenty-nine patients (56%) had idiopathic osteoporosis and 23 (44%) had secondary osteoporosis. Fifteen patients (29%) had vertebral fractures and 12 had previous peripheral fractures. Patients with secondary osteoporosis showed higher BMI (23.2 +/- 3 v 21.2 +/- 2, P =.02) and lower femoral Z-scores of bone mineral density (BMD) (-2.1 +/- 0.6 v -1.5 +/- 0.9, P =.02) than those with idiopathic disease. The most frequent causes of secondary osteoporosis included Cushing syndrome, pregnancy osteoporosis, and osteogenesis imperfecta. Nearly half of the patients (48%) with idiopathic osteoporosis had a family history of osteoporosis. In addition, 11 patients (38%) with idiopathic osteoporosis had associated hypercalciuria. Except for an increase in urinary calcium excretion (248 +/- 53 v 143 +/- 47 mg/24 h, P <.0001), no other significant differences in the remaining variables analyzed were found between hypercalciuric and normocalciuric patients with idiopathic osteoporosis. CONCLUSIONS: Idiopathic osteoporosis was the most frequent diagnosis of pre-menopausal osteoporosis in our unit. These patients showed lower BMI and higher femoral neck Z-scores than patients with secondary causes. A family history of osteoporosis and hypercalciuria were factors frequently associated with this disorder.     

Femoral bone mineral density is associated with vertebral fractures in patients with ankylosing spondylitis: a cross-sectional study

OBJECTIVE: To determine the association between vertebral fractures and clinical, laboratory, and radiological variables in patients with ankylosing spondylitis (AS). METHODS: Sixty-eight men with AS and 91 sex- and age-matched controls were consecutively enrolled. Vertebral fractures were assessed according to a visual semiquantitative grading system using plain radiographs of the lumbar spine obtained from patients with AS. Disease activity variables including C-reactive protein, erythrocyte sedimentation rate, finger-to-ground distance score, Schober's Index score, Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s) score, and syndesmophyte score were identified. Assessments of bone mineral density (BMD) of the lumbar spine and the femur in patients and controls were performed using an anteroposterior dual energy x-ray absorptiometry technique. RESULTS: Eleven patients (16.2%) out of the total of 68 patients with AS had vertebral fractures; these were identified as wedge deformities (n = 5) or biconcave (n = 6) deformities. BMD levels of the lumbar spine and femur in patients were significantly reduced compared with those of age-matched controls. There were significant differences in the Schober's Index scores, finger-to-ground distance scores, BASRI scores of the lumbar spine, syndesmophyte scores, and intertrochanter values of BMD among AS patients both with and without vertebral fractures. Multiple logistic regression analyses revealed that intertrochanteric BMD values also were independently associated with vertebral fractures in AS (p = 0.041). CONCLUSION: We demonstrated evidence of a correlation between low femoral BMD levels and risk of vertebral fractures in patients with AS, especially at the intertrochanteric area. Longitudinal studies in a large population are required to determine the diagnostic implications of femur BMD for increased risk of vertebral fractures in AS.     

Bone mineral density and fractures in Turner syndrome

PURPOSE: To determine whether women with Turner syndrome who were treated with estrogen were more likely to have osteoporosis and fractures. METHODS: Areal bone density at the lumbar spine and femoral neck was measured in 40 adult women with Turner syndrome and 43 age-matched healthy women using dual-energy X-ray absorptiometry. Histories of estrogen treatment and fractures were obtained by structured personal interviews. RESULTS: Mean (+/- SD) areal bone density was significantly lower at the lumbar spine (0.87 +/- 0.11 g/cm(2) vs. 0.98 +/- 0.10 g/cm(2), P <0.001) and femoral neck (0.68 +/- 0.07 g/ cm(2) vs. 0.83 +/- 0.08 g/cm(2), P <0.001) in women with Turner syndrome than in controls. The diagnostic criterion for osteoporosis (T-score <-2.5) was met by 8 women with Turner syndrome (20%) with scores at the lumbar spine and by 3 (8%) with scores at the femoral neck. All women diagnosed with osteoporosis were less than 150 cm in height. Areal bone density correlated significantly with height (lumbar spine: R(2) = 0.3, P <0.001; femoral neck: R(2) = 0.4, P <0.001). Adjustments for skeletal size reduced the differences between the groups as well as the number of women diagnosed with osteoporosis (e.g., from 8 to 2 women based on lumbar spine scores). The prevalence and type of fractures were similar in the two groups. CONCLUSIONS: The prevalence of osteoporosis and bone fractures is not increased significantly in women with Turner syndrome who are treated with standard estrogen therapy. Women less than 150 cm in height are likely to be misdiagnosed with osteoporosis when areal bone density is measured, unless adjustments for body size are made.     

Incidence of vertebral fractures in the first three months after orthotopic liver transplantation

BACKGROUND AND OBJECTIVES: High rates of bone loss and increased fracture incidence have been reported in patients undergoing liver transplantation, mainly within the first post-operative year. The pathogenesis of post-transplantation bone disease has not been clearly established, but the high doses of glucocorticoids used for immunosuppression may contribute. The use of lower doses in recent years has been associated, in some studies, with lower rates of bone loss and decreased fracture incidence. The aim of this prospective study was to establish the incidence of vertebral fractures in the first 3 months in patients undergoing liver transplantation for chronic liver disease and to identify risk factors for fracture in these patients. DESIGN AND METHODS: Thirty-seven adults with end-stage liver disease were studied prospectively prior to and 3 months after liver transplantation. Vertebral fractures were assessed semi-quantitatively from lateral spine X-rays and bone mineral density measured using dual energy X-ray absorptiometry. RESULTS: Prior to transplantation, prevalent vertebral fractures were present in 13 patients (35%). New fractures developed after transplantation in 10 patients (27% of total) and were significantly more common in those with a prevalent vertebral fracture pre-operatively (P<0.02). Osteoporosis, defined as a bone mineral density T score below -2.5, was present in 39% of patients prior to transplantation, but bone mineral density was not helpful in predicting incident fracture, whether measured before or after transplantation. Over the 3-month study period, significant bone loss occurred in the femoral neck (P<0.05) but not the lumbar spine. CONCLUSIONS: Our results demonstrate a high incidence of vertebral fracture in the first 3 months after liver transplantation and indicate that prevalent vertebral fracture is an important risk factor for the subsequent development of fracture in these patients. Prevention of post-transplantation bone disease should focus both on optimizing bone mass prior to transplantation and preventing bone loss in the early post-operative period.     

Parathyroid hormone deficiency and excess: similar effects on trabecular bone but differing effects on cortical bone

Parathyroid hormone (PTH) may be anabolic at trabecular bone and catabolic in cortical bone. As many regions of the skeleton contain both types of bone, the effects of PTH deficiency or excess may be difficult to evaluate using bone densitometry, a technique that integrates the cortical and trabecular compartments of bone. We asked the following questions: 1) Is the higher bone mineral density (BMD) in postsurgical hypoparathyroidism due to higher cortical, not trabecular, bone? 2) Is age-related bone loss slowed in patients with postsurgical hypoparathyroidism? 3) Is lower BMD in primary hyperparathyroidism the result of deficits in cortical, not trabecular, bone? BMD of the lumbar spine, proximal femur, distal radius, and femoral midshaft was measured by postero-anterior (PA) scanning, while bone mineral content (BMC) of the third lumbar vertebra was measured by lateral scanning using dual x-ray absorptiometry in 10 women, ages 64.6 +/- 3.2 yr, with postsurgical hypoparathyroidism and in 25 women, ages 68.7 +/- 1.6 yr, with primary hyperparathyroidism. Measurements were repeated 4.7 +/- 0.6 yr later in 8 patients with hypoparathyroidism and 4.0 +/- 0.4 yr later in 20 age-matched controls. Data were expressed as z scores (SD, mean +/- sem) derived from 405 postmenopausal women. In patients with hypoparathyroidism, bone mass z score of the third lumbar vertebra (vertebral body plus posterior processes) was higher than zero by PA scanning (1.26 +/- 0.58 SD, P < 0.05) and lateral scanning (1.04 +/- 0.60 SD, P = 0.1), and higher at the trabecular-rich vertebral body (1.02 +/- 0.47 SD, P = 0.07) and predominantly cortical posterior processes (0.98 +/- 0.66 SD, P = 0.1) determined by lateral scanning. The BMD z scores were higher than zero at the femoral neck (0.89 +/- 0.48 SD, P = 0.09), but not at the femoral midshaft (0.45 +/- 0.60, NS) and distal radius (0.04 +/- 0.51, NS). During follow-up, femoral neck BMD decreased in controls but not in patients with hypoparathyroidism (slope, -0.00818 +/- 0.00496 g/cm2/year vs. 0.00907 +/- 0.00583 g/cm2/year, respectively, P = 0.06). There was no change in lumbar spine BMD in either group. In 25 women with primary hyperparathyroidism, there were no deficits in BMD at the third lumbar vertebra (vertebral body plus posterior processes) by PA or lateral scanning. By lateral scanning, BMC was increased at the vertebral body (0.64 +/- 0.31 SD, P < 0.01) and reduced at the posterior processes (-0.65 +/- 0.26 SD, P < 0.05). BMD was lower at the midshaft of the femur (-0.82 +/- 0.37 SD, P < 0.05) and at the distal radius (-0.68 +/- 0.20 SD, P < 0.01), but not at the femoral neck (-0.08 +/- 0.20 SD, NS). Longitudinal data were unavailable in hyperparathyroid patients. In summary, trabecular bone is increased by both PTH deficiency and excess. Cortical bone loss is slowed by PTH deficiency and accelerated by PTH excess so that suppression of PTH may reduce age-related bone loss and the risk of fracture. Assessment of BMD in PTH deficiency and excess requires the separate study of cortical and trabecular bone.     

Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

OBJECTIVE: Risedronate, a new pyridinyl bisphosphonate, is a potent antiresorptive bone agent. This study examines the safety and efficacy of daily, oral risedronate therapy for the prevention of corticosteroid-induced bone loss. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted in 224 men and women who were initiating long-term corticosteroid treatment. Patients received either risedronate (2.5 mg or 5 mg) or placebo daily for 12 months. Each patient also received 500 mg of elemental calcium daily. The primary outcome measure was the percentage of change in lumbar spine bone mineral density (BMD). Secondary measures included proximal femur BMD and incidence of vertebral fractures. RESULTS: After 12 months, the lumbar spine BMD (mean +/- SEM) did not change significantly compared with baseline in the 5-mg (0.6 +/- 0.5%) or the 2.5-mg (-0.1 +/- 0.7%) risedronate groups, while it decreased in the placebo group (-2.8 +/- 0.5%; P < 0.05). The mean differences in BMD between the 5-mg risedronate and the placebo groups were 3.8 +/- 0.8% at the lumbar spine (P < 0.001), 4.1 +/- 1.0% at the femoral neck (P < 0.001), and 4.6 +/- 0.8% at the femoral trochanter (P < 0.001). A trend toward a decrease in the incidence of vertebral fracture was observed in the 5-mg risedronate group compared with the placebo group (5.7% versus 17.3%; P = 0.072). Risedronate was well tolerated, and the incidence of upper gastrointestinal adverse events was comparable among the 3 groups. CONCLUSION: Risedronate therapy prevents bone loss in patients initiating long-term corticosteroid treatment.     

Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance

The possible relationships between biochemical measurements and both densitometric and radiographic indexes of skeletal fragility were evaluated in 65 postmenopausal women with monoclonal gammopathy of undetermined significance (MGUS). There was a significantly higher prevalence of vertebral fractures in the MGUS group compared with a control population (P < or = 0.001). The MGUS patients were then grouped according to the presence or absence of at least one mild vertebral fracture. Patients with fractures (Fx, n=34) were older (62.8 +/- 6.1 years), with long-standing disease (8.8 +/- 7.1 years) when compared with those without fractures (NFx, n=31; 59.7 +/- 5.0 years, P < or = 0.05 and 5.8 +/- 4.1 years, P < or = 0.05). The receptor activator of nuclear factor kappa-B ligand/osteoprotegerin ratio was higher in Fx compared with NFx (0.092 +/- 0.018 vs. 0.082 +/- 0.020; P < or = 0.05). Lumbar spine (0.811 +/- 0.14 vs. 0.956 +/- 0.12 g/cm2), femoral neck (0.660 +/- 0.09 vs. 0.747 +/- 0.10 g/cm2) and total bone mineral density (BMD) (0.788 +/- 0.11 vs. 0.884 +/- 0.11 g/cm2) were lower (all P < or = 0.001) in FxMGUS compared with Nfx patients. Receiver operating characteristic curves identified lumbar BMD as the variable that best predicted vertebral fractures (area under the curve 0.817; 95% confidence interval, 0.713-0.921). This study provides an indication for the measurement of BMD in MGUS patients, as a means of predicting vertebral fractures, especially in those that are asymptomatic. Patients with prevalent fractures should undergo pharmacological treatment to prevent further fractures.