Reversible sclerotic changes of lumbar spine and femur due to long-term oral isotretinoin therapy

We present a rare case of retinoid-induced sclerotic changes of lumbar spine and femur demonstrated by dual energy x-ray absorptiometrie (DEXA). The patient had flowing ossification along thoracic spine resembling diffuse idiopathic skeletal hyperostosis (DISH), but there was no ligament calcification in the lumbar spine or pelvis. After discontinuation of the treatment, gradual decline of bone mineral density at lumbar and femoral sites was detected with serial DEXA measurements. To the best of our knowledge, although various abnormalities of bone due to retinoids have been described before, reversible sclerotic changes have not been reported.     

Approach to the prostate cancer patient with bone disease

Prostate cancer is the most common visceral malignancy in men. Androgen deprivation therapy (ADT) is commonly used in patients with nonmetastatic prostate cancer and is associated with significant bone loss and fractures. The greatest bone loss occurs during initiation of ADT. Men should have assessment of skeletal integrity with bone mineral density examination by dual x-ray absorptiometry of the hip and spine. Men with fragility fractures or osteoporosis by bone density should be considered for bisphosphonate therapy. Men with low bone mass may need antiresorptive therapy, depending on other risk factors. Men with a normal bone mineral density should be followed up closely with bone densitometry while on ADT. All men should receive preventive measures with calcium (1200 mg daily in divided doses), vitamin D (800-1000 IU/d), and weight-bearing exercise. Men should be evaluated for additional secondary causes of bone loss including vitamin D insufficiency. Guidelines are needed for androgen-induced bone loss screening and treatment.     

Cushing's Syndrome and Bone

Structural and functional impairment of skeletal system is a relevant cause of morbidity and disability in patients with Cushing's syndrome (CS). Approximately 30–50% of patients with CS experience fractures (particularly at the spinal level) consistent with the 50% incidence of osteoporosis. Growth failure, pubertal arrest are the hallmarks of CS in children and growing adolescents leading to reduced final adult height and peak bone mass. The decrease in osteoblast number and function, through different mechanisms, seems to play a central role in the bone loss in CS. Patients with CS have decreased serum levels of osteocalcin and alkaline phosphatase. Considering the preferential bone loss in the cancellous skeleton it is reasonable to measure BMD, possibly with Dual X-rays absorptiometry (DEXA) at lumbar spine, in all patients with CS. Patients cured from CS have increased prevalence of spine damage: therefore, a radiological follow-up of the skeleton should be included in the management of patients with CS not only during the active phase but also after cure. Glucocorticoid-induced osteoporosis is reversible. The recovery of bone loss in CS is slow, taking approximately ten years to become complete. In the meanwhile, patients with severe osteopenia are exposed to a high risk of fracture. Alendronate may induce a more rapid improvement in BMD than cortisol normalization alone and it could be useful in patients with persistent postsurgical hypercortisolism to prevent further bone loss. The decision to discontinue antiresorptive therapy should be based on clinical monitoring and DEXA measurements.     

女性2型糖尿病患者骨密度调查与评估

目的观察女性2型糖尿病（T2DM）患者的骨密度（BMD）变化，探讨BMD数据比较的方法。方法选取女性T2DM患者484例，健康女性志愿者868例，测量正侧位腰椎2至4的椎体、左侧股骨颈、大转子和Ward三角区BMD。确立健康女性各骨骼部位BMD随年龄的变化关系，以三次回归模型建立数据库。结果（1）糖尿病组BMD值与正常人比较无统计学差异。（2）与峰值BMD比较，糖尿病组随年龄增加BMD值下降，且受累骨骼部位增加。（3）同年龄组糖尿病和正常人与峰值骨量差值比较，差异无统计学意义。结论T2DM患者BMD变化与正常人群无统计学差异；比较与峰值骨量的差值是判断骨质疏松程度的标准。     

Gender, age, and body weight are the major predictive factors for bone mineral density in Crohn's disease: a case-control cross-sectional study of 113 patients

OBJECTIVE: We conducted this study to assess bone mineral density and to evaluate conceivable predictive factors for bone loss in patients with Crohn's disease. METHODS: One hundred-thirteen patients with Crohn's disease and 113 healthy subjects, individually matched for gender, age, and body weight were investigated. The group consisted of 68 women and 45 men. The median duration of Crohn's disease was 6 yr. Two-thirds of the patients had been subjected to intestinal resection. Seventy-seven percent had at some time been treated with corticosteroids. Bone mineral density in the lumbar spine, the hip, and the total body skeleton was measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: In patients with Crohn's disease bone mineral density was not different from that of healthy controls except for a regional decrease in bone mineral density of the hip in female patients. The strongest predictors of bone mineral density were gender, age, and body weight. Corticosteroid use was only a weak predictor of diminished bone density. Duration of disease and intestinal resection had no predictive value for bone mineral density. CONCLUSIONS: Gender, age, and body weight are the major determinants of bone mineral density in patients with Crohn's disease. As in healthy individuals, the combined effect of these factors account for up to 50% of the variability in bone mineral density.     

Bone loss is detected more frequently in patients with ankylosing spondylitis with syndesmophytes

OBJECTIVE: To define the relationship between bone growth (syndesmophytes) and bone loss (osteoporosis) in ankylosing spondylitis (AS). METHODS: Bone mineral density (BMD) at the spine, hip, and radius was measured by dual-energy x-ray absorptiometry (DEXA), dual-energy quantitative computed tomography (DEQCT), and peripheral quantitative computed tomography (pQCT) in 103 patients with AS. Radiographs of the lumbar spine were used to detect syndesmophytes. Patients were divided in 3 groups according to disease duration. RESULTS: Osteopenia at the hip and spine was found by DEXA in 56% and 41%, respectively, of the patients with disease duration < 5 years (n = 27), with an additional 11% and 15% having osteoporosis. In patients with a longer disease duration, > 10 years (n = 28), 29% were osteoporotic at the hip and only 4% at the lumbar spine. In contrast, using spinal DEQCT, 59% of patients with early disease were found to be osteopenic; 36% of patients with long-standing disease were osteopenic and 18% were osteoporotic. More than half the patients (55%) had syndesmophytes (n = 55). With spinal DEQCT there were more patients with syndesmophytes (63%) in the group with reduced bone density than in the group without (45%). This was similar with DEXA measurements at the hip, where 31% compared to 14% had osteoporosis, respectively. Osteocalcin was elevated in 34% of patients, but was not associated with disease activity or BMD. CONCLUSION: The majority of patients with AS had reduced bone density. The method of bone density measurement is critical and should be different depending on disease duration. The finding that more patients with syndesmophytes had reduced bone density than those without suggests that bone growth and bone loss occur in parallel, and the role of inflammation in this process warrants further investigation.     

Dual-energy X-ray absorptiometry in clinical practice and its trouble spots in bone mineral measurement

The technique of dual energy X-ray absorptiometry (DXA) is widely used for bone mineral density (BMD) measurement at present. BMD at PA spine should be measured for diagnosis of osteoporosis in all patients. If BMD at PA spine is inappropriate for the evaluation, proximal femur is selected for the measurement site. Various clinical issues pertained to this technique have been known. This paper reviewed clinical practice and trouble spots of BMD measurements at AP spine, proximal femur, and distal forearm.     

Relation between insulin-like growth factor-I concentrations, osteoarthritis, bone density, and fractures in the general population: the Chingford study.

OBJECTIVE: To assess the association between serum insulin-like growth factor-I (IGF-1) concentrations and osteoarthritis, and bone mineral density, and fractures in a large group of middle aged women from the general population. METHODS: 761 women aged 44-64 years from the Chingford study had serum IGF-I concentrations measured; hand, hip, spine, and anteroposterior weight bearing knee radiographs taken; and dual energy x ray absorptiometry (DEXA) scans of the hip and spine. X rays were scored using the Kellgren and Lawrence system. In addition knee x rays were scored using a standard atlas for individual features of osteophytes and joint space narrowing (both graded 0-3). IGF-I concentrations were adjusted for the effects of age. RESULTS: In the osteoarthritis analysis results were compared to a constant group of 155 subjects with no evidence of osteoarthritis at any site. There was no significant difference in serum IGF-I between these subjects and 606 subjects with osteoarthritis at any site. When individual sites were analysed, serum IGF-I was higher in those cases with more severe bilateral knee osteoarthritis and in those with distal interphalangeal (DIP) joint disease. There was no significant association between serum IGF-I and other forms of osteoarthritis or milder forms of knee osteoarthritis. There was no correlation between IGF-I concentrations and bone mineral density at the spine or hip, nor any difference between IGF-I concentrations in subjects with and without a history of non-traumatic fracture [22.8 (SD 6.6) v 23.1 (SD 6.6) nmol litre-1, P = 0.6] CONCLUSIONS: There is a modest association between IGF-I concentrations and the development of DIP osteoarthritis and more severe or bilateral knee joint osteoarthritis in women from the normal population, but no association with other forms of osteoarthritis, bone density, or fractures.     

Peripheral bone densitometry: Clinical applications

Technologies for the measurement of bone mineral density and other parameters of bone strength at peripheral skeletal sites have been studied since the 1960s. Single-energy Photon Absorptiometry (SPA), Radiographic Absorptiometry (RA), Radiogrametry (RG), Single-energy X-ray Absorptiometry (SXA), Peripheral Dual-energy X-ray Absorptiometry (pDXA), and Quantitative Ultrasonometry (QUS) have been successively evaluated. These technologies and their clinical applications are discussed in this article. The available scientific evidence supports the clinical use of these technologies at peripheral skeletal for assessment of fracture risk. Peripheral measurements other than the 33% (one-third) radius by DXA cannot be used to diagnose osteoporosis according to current standards. Peripheral skeletal sites are not clinically useful for monitoring changes in BMD with natural evolution of the disease and its treatment. Peripheral BMD measurement can theoretically be used to screen patients for selection to central DXA testing, although device-specific cut-points should be developed before this is implemented. When central DXA testing is not available, peripheral BMD testing may be considered to identify individuals who might benefit from pharmacological intervention.     

Pattern of bone mineral density in idiopathic male osteoporosis

The mechanisms of male idiopathic osteoporosis are little known. We evaluated bone mineral loss by dual-energy X-ray absorptiometry and determined its cortical or trabecular nature in a cohort of men with idiopathic osteoporosis with fractures. Thirty-nine men (mean age 60?±?13?years), with negative investigations for the cause of osteoporosis, were studied. All had fragility fractures: vertebral 51%, peripheral 25%, and both types 24%. Bone density was measured at the lumbar spine (L2-L4), total hip and whole body. The limb/axial skeleton (spine?+?hips) and hip/L2-L4 BMD ratios were calculated. Serum 25-hydroxy-vitamin D, PTH, bone alkaline phosphatase and CTX were measured. Bone mineral loss predominated at the lumbar spine (mean L2-L4 T-score -3?±?0.93, mean total hip T-score -1.87?±?0.75). Limb/axial skeleton and total hip/L2-L4 BMD were strongly correlated, but not hip and spine BMD. The ratio values were widely scattered, indicating markedly heterogeneous bone loss. Vitamin D, PTH, bone alkaline phosphatase and CTX levels did not differ between predominantly trabecular and cortical osteoporosis. Bone mineral density measurement in male idiopathic osteoporosis with fractures demonstrated that bone loss predominated in the spine and that it was very heterogeneous, principally affecting cortical or trabecular bone depending on the patient.     

Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis.

Atraumatic fractures caused by osteoporosis may be a serious complication of primary biliary cirrhosis. Mean (+/- S.D.) bone mineral density in the lumbar spine in 210 ambulatory women with primary biliary cirrhosis was 1.02 +/- 0.19 gm/cm2, 7% lower than that in 139 age-matched normal women (after adjustment for age and body weight) (p less than 0.001). Bone mineral density in the lumbar spine was inversely related to a risk score index of liver disease severity (r = -0.29, p less than 0.001). The mean rate of bone loss in 105 of these 210 women was 2%/yr +/- 4%/yr, twice as great as in the 139 normal women (p less than 0.02). In 20 women with primary biliary cirrhosis followed up after orthotopic liver transplantation, bone mineral density in the lumbar spine decreased at 3 mo (p less than 0.01), and this decrease may have resulted in atraumatic fractures in 13 of them. Bone mineral density in the lumbar spine then increased (p less than 0.01) so that by 12 mo the median bone mineral density in the lumbar spine was similar to that before transplantation and by 24 mo it was 5% above it. Therefore we conclude that the progressive bone loss observed in primary biliary cirrhosis (which is further accentuated immediately after transplantation) may be halted, and the bone mass may be restored toward normal within 2 to 3 yr after orthotopic liver transplantation.     

Concentration of insulin-like growth factor (IGF)-I in iliac crest bone matrix in premenopausal women with idiopathic osteoporosis.

Previous studies have shown a link between low serum insulin-like growth factor-I (IGF-I) and decreased bone mass of patients with osteoporosis. However, whether serum levels are representative for the growth factor concentration or activity available in human bone tissue is controversial. In the present study, IGF-I was assessed in serum and bone matrix extracts from the iliac crest in 19 eugonadal women with idiopathic osteoporosis and in 38 age-matched controls. In addition, the relationship between the skeletal levels of IGF-I and bone mineral density (BMD) or the susceptibility to osteoporotic fractures in women with osteoporosis was examined. Bone matrix extraction was performed based on a guanidine-HCL/ethylendiamine-tetraacetic acid (EDTA) method. No significant difference in both serum and bone matrix IGF-I levels between groups was observed. Serum IGF-I concentrations failed to be associated with bone matrix IGF-I levels in osteoporotic patients. However, in premenopausal women with idiopathic osteoporosis, skeletal IGF-I positively correlated with BMD at the lumbar spine (r = + 0.58, p = 0.01). In contrast, neither femoral neck BMD nor Ward's triangle BMD was associated with bone matrix IGF-I concentrations. A tendency towards lower levels of bone matrix IGF-I in subjects with vertebral fractures as compared to those without fractures was observed in age-adjusted analyses, however the difference failed to remain statistically significant after adjustment for bone mineral density. These data provide no clear evidence for low bone matrix IGF-I as a determinant factor of age-unrelated osteoporosis. However, low skeletal IGF-I concentrations may aggravate osteoporosis in these women.     

Aging bone loss from the femur, spine, radius, and total skeleton

In order to establish a comprehensive model for involutional bone loss, the following measurements were made of healthy white women: total body calcium by neutron activation analysis, bone density of the distal radius by single-photon absorptiometry, and dual-photon absorptiometry of the lumbar spine and femur (neck, Ward's triangle, and intertrochanteric areas). Longitudinal measurements were made for each of these skeletal sites except the femur. Evidence for a curvilinear component to the pattern of bone loss with aging was found for total body calcium and bone density of the radius, but not for the other measurements on analysis of cross-sectional data. Longitudinal studies confirmed that substantial bone loss begins only after menopause for the radius, whereas there is substantial premenopausal loss of bone from the lumbar spine. Prevention of vertebral osteoporosis requires maximizing bone mass before menopause. If longitudinal data confirm the model of linear rates of bone loss for the femur, there will be important implications for prevention of hip fractures.     

The threshold of bone mineral density for vertebral fractures in female patients with primary hyperparathyroidism

BACKGROUND AND OBJECTIVE: Primary hyperparathyroidism (pHPT) is one of the causal diseases that induce secondary osteoporosis. Although patients with pHPT have reduced bone mineral density (BMD) especially at the cortical bone, there have been controversies about risk of fracture. Moreover, no reports have been available about the threshold of BMD for fractures in pHPT patients. METHODS: BMD values were measured by dual-energy x-ray absorptiometry at lumbar spine, femoral neck and distal one third of radius. Various indices were compared in 116 female pHPT patients and 716 control subjects. Moreover, we analyzed relationship between the cut-off values of BMD and the prevalence of vertebral fractures in pHPT and control subjects. RESULTS: The prevalence of subjects with vertebral fractures was lower in pHPT patients, compared with that of control subjects. Age and body height were significantly higher and lower in pHPT women with vertebral fractures, respectively. Lumbar spine BMD was significantly lower in pHPT women with vertebral fractures, presumably due to their increased age. There were no differences in femoral neck and radius BMD or in bone metabolic indices between pHPT women with and without vertebral fractures. On the other hand, age-matched BMD was not significantly different between both groups at any measured site. Cut-off values of BMD at lumbar spine and femoral neck were lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group. Moreover, cut-off values of BMD at radius was much lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group (pHPT vs control (g/cm(2)): 0.670 vs 0.706 at lumbar spine; 0.549 vs 0.570 at femoral; 0.394 vs 0.474 at radius). Sensitivity and specificity of vertebral fractures was lower in pHPT patients, compared with those in control group. CONCLUSIONS: The present cross-sectional study demonstrated that thresholds of BMD for vertebral fractures were lower especially at radial bone in female patients with pHPT, compared with those in the control group.     

A prospective evaluation of bone mineral density measurement in females who have fallen

BACKGROUND: The National Service Framework for Older Persons recognises the relationship between falls and osteoporosis; however, the best method for the evaluation of bone mineral density measurement in fallers is unclear. Dual energy X-ray absorptiometry of lumbar spine and hip is the gold standard for bone mineral density measurement, but is time consuming and may not be readily available. A cheaper, more portable alternative is peripheral dual energy X-ray absorptiometry of the heel. This predicts overall fracture risk as effectively as dual X-ray at the spine and hip, although site specific measurements provide the best estimate of fracture risk at a particular location. AIMS: 1. To validate peripheral dual energy X-ray in fallers by comparing heel bone mineral density measurement with measurements obtained at the lumbar spine and hip. 2. To determine the prevalence of osteoporosis in an unselected cohort of fallers. METHODS: 118 consecutive females over 50 attending for investigation of falls had heel bone mineral density measurement measured using peripheral dual energy X-ray (PIXI, Lunar). A representative sample of 52 (44%) also attended for bone mineral density measurement at the hip and lumbar spine using Hologic QDR 4500. Bone mineral density (g/cm(2)) measurements were compared with mean values for young adults and age-related normals giving T (number of standard deviation units above or below the mean for normal young adults) and Z (number of standard deviations above or below the age-related normal mean) scores. RESULTS: In the total group [n = 118 mean (SD) age 74 (11)] heel bone mineral density was 0.4 (0.1), T score--1.1 (1.6) and Z score--0.1 (1.5). The relationship between absolute bone mineral density measurements taken at heel, total hip and lumbar spine were compared and the correlation coefficients show a strong positive relationship between all measurements (all r values > 0.54, P < 0.0001) with a particularly strong relationship between hip and heel (r = 0.74). Those with two or more risk factors for falls were significantly more likely to have lower bone mineral density. DISCUSSION: This study has shown that peripheral dual energy X-ray is a reliable method of assessment, applicable to use within a Falls Unit. In addition, although the prevalence of osteoporosis is not increased in unselected fallers, those with two or more risk factors for falls are at increased risk of osteoporosis and limited resources may be more appropriately targeted toward this group.     

Single-site vs multisite bone density measurement for fracture prediction

BACKGROUND: Bone density measurement with dual-energy x-ray absorptiometry is widely used for fracture risk assessment. Discordance between measurement sites is common, but it is unclear how this affects fracture prediction. METHODS: We performed a historical cohort study among 16 505 women 50 years or older at the time of baseline dual-energy x-ray absorptiometry of the spine and hip (mean +/- SD observation period, 3.2 +/- 1.5 years). The study population was drawn from a database that contains all clinical dual-energy x-ray absorptiometry test results for the province of Manitoba, Canada. Each subject's longitudinal health service record was assessed for the presence of fracture codes after bone density testing. The likelihood ratio test was used to assess the improvement in fracture prediction from Cox proportional hazards models using bone density covariates from a single site or from combined sites. RESULTS: Age-adjusted hazard ratios (HRs) per standard deviation for osteoporotic fracture ranged from 1.61 (95% confidence interval [CI], 1.39-1.87) for the lumbar spine to 1.85 (95% CI, 1.70-2.01) for the total hip, with intermediate values for the femur neck (HR, 1.76 [95% CI, 1.62-1.92]) and trochanter (HR, 1.77 [95% CI, 1.63-1.92]). For fracture prediction, use of the minimum bone density measurement was no better than use of a hip measurement alone. When the total hip measurement was included in a fracture prediction model for the overall population, none of the other measurements added substantial information. The spine was the most useful site for the prediction of spine fractures alone. CONCLUSIONS: Proximal femur bone density measurements consistently outperformed lumbar spine measurements for global fracture prediction. In this cohort, the total hip was the best site for overall fracture assessment.     

Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial

CONTEXT: In preclinical models, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase have been shown to positively affect bone remodeling balance. Observational studies and secondary analyses from lipid-lowering trials have yielded inconsistent results regarding the effect of these agents on bone mineral density and fracture risk. OBJECTIVE: Our objective was to determine whether clinically significant skeletal benefits result from hydroxymethylglutaryl-coenzyme A reductase inhibition in postmenopausal women. DESIGN AND SETTING: We conducted a prospective, randomized, double-blind, placebo-controlled, dose-ranging comparative clinical trial at 62 sites in the United States. PARTICIPANTS: Participants included 626 postmenopausal women with low-density lipoprotein cholesterol levels of at least 130 mg/dl (3.4 mmol/liter) and less than 190 mg/dl (4.9 mmol/liter), and lumbar (L1-L4) spine bone mineral density T-score between 0.0 and -2.5. INTERVENTION: Once-daily placebo or 10, 20, 40, or 80 mg atorvastatin was administered. MAIN OUTCOME MEASURES: We assessed percent change from baseline in lumbar (L1-L4) spine bone mineral density with each dose of atorvastatin compared with placebo. RESULTS: At 52 wk, there was no significant difference between each atorvastatin and placebo group or change from baseline at any tested dose of atorvastatin or placebo in lumbar (L1-L4) spine bone mineral density. Nor did atorvastatin produce a significant change in bone mineral density at any other site. Changes in biochemical markers of bone turnover did not differ significantly between each atorvastatin and placebo group. All doses of atorvastatin were generally well tolerated, with similar incidences of adverse events across all dose groups and placebo. CONCLUSIONS: Clinically relevant doses of atorvastatin that lower lipid levels had no effect on bone mineral density or biochemical indices of bone metabolism in this study, suggesting that such oral agents are not useful in the prevention or treatment of osteoporosis.     

Measurement of spinal or peripheral bone mass to estimate early postmenopausal bone loss?

This report presents data from 153 healthy, early postmenopausal women who were randomly allocated to two years of treatment with estrogen or placebo. Bone mineral content in the forearms was measured by single-photon absorptiometry, and bone mineral density of the lumbar spine and total-body bone mineral by dual-photon absorptiometry, before and after one and two years of treatment. At the end of the two years, there were highly significant differences of 6 to 7 percent between the estrogen and the placebo groups at all sites measured. The range of the changes of the spine measurement was twice that of the forearm and total-body measurements. It is concluded that measurement of the forearm by single-photon absorptiometry is superior to measurement of the spine by dual-photon absorptiometry both in clinical studies and in the individual patient for detecting estrogen-dependent bone loss and its treatment by estrogen replacement.     

Paget's disease of bone

Paget's disease of bone is defined as a process of increased bone remodeling; the primary event is increased resorption (osteoclastic activity) followed by subsequent reactive bone formation (osteoblastic activity). It is usually asymmetric and may be asymptomatic. The etiology is unknown, but recent evidence appears to support the theory that a virus is an important etiologic factor. It may present with a wide variation in the clinical and radiographic picture. The most frequent sites of involvement include the spine, femora, cranium, pelvis, and sternum. The most common complaints are pain, skeletal deformity, and change in skin temperature. Pathologic fractures may be the presenting manifestations or complications in a patient with known Paget's disease. They occur most frequently in the long weight-bearing bones of the lower extremities such as the femoral neck and subtrochanteric and tibial regions. The two major therapeutic agents available for treatment are calcitonins (porcine, salmon, or human) and diphosphonates. The aim of such therapy is to control the metabolic activity of the disease, to normalize the biochemical parameters, and to improve the symptoms. Fortunately, tumors are rare; early diagnosis may give rise to more effective palliation, if not a significant cure rate.     

Effect of pamidronate on new vertebral fractures and bone mineral density in patients with malignant lymphoma receiving chemotherapy

BACKGROUND: High doses of corticosteroids, and the use of alkylating agents like cyclophosphamide with subsequent hypogonadism, have been implicated in the pathogenesis of chemotherapy-induced osteoporosis. In this study, we evaluated whether intravenous pamidronate can prevent bone loss and reduce vertebral fractures in patients with malignant lymphoma who were receiving chemotherapy. METHODS: We enrolled 50 patients who had newly diagnosed stage III or IV malignant lymphoma. All patients were assigned randomly to receive either intravenous pamidronate or placebo. Pamidronate (30 mg per treatment) or placebo was given at 3-month intervals for 12 months. Five patients in the control group dropped out during the trial. The main outcomes were the incidence of vertebral fractures and changes in bone mineral density of the lumbar spine and proximal femur. RESULTS: During the 12-month study, 6 (30%) of the 20 patients in the control group and 1 (4%) of the 25 patients in the pamidronate group developed new vertebral fractures (P = 0.01). In the control group, the mean percentage changes in bone mineral density were -11.2% in the lumbar spine and -4.5% in the femoral neck. In contrast, pamidronate treatment led to minor losses of bone mineral density at both sites (-2.7% at the lumbar spine; -2.3% at the femoral neck). The difference between the groups was significant at the lumbar spine (P = 0.005). CONCLUSION: Pamidronate reduces trabecular bone loss and the risk of new vertebral fractures in patients with malignant lymphoma receiving chemotherapy.