Quantitative computed tomography of the lumbar spine,not dual x‐ray absorptiometry,is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long‐term glucocorticoid and hormone‐replacement therapy

Objective

To determine which measurement of bone mineral density (BMD) predicts vertebral fractures in a cohort of postmenopausal women with glucocorticoid‐induced osteoporosis.

Methods

We recruited 114 subjects into the study. All had osteopenia of the lumbar spine or hip, as demonstrated by dual x‐ray absorptiometry (DXA), and were receiving long‐term glucocorticoids and hormone replacement therapy (HRT). Measurements of BMD by DXA of the lumbar spine, hip (and subregions), and forearm (and subregions), quantitative computed tomography (QCT) of the spine and hip (n = 59), and radiographs of the thoracolumbar spine were performed on all subjects to assess prevalent vertebral fractures. Vertebral fracture prevalence, as determined by morphometry, required a ≥20% (or ≥4‐mm) loss of vertebral body height. Demographic information was obtained by questionnaire. Multiple regression and classification and regression trees (CART) analyses were used to assess predictors of vertebral fracture.

Results

Twenty‐six percent of the study subjects had prevalent fractures. BMD of the lumbar spine, total hip and hip subregions, as measured by QCT, but only the lumbar spine and total hip, as measured by DXA, were significantly associated with prevalent vertebral fractures. However, only lumbar spine BMD as measured by QCT was a significant predictor of vertebral fractures. CART analysis showed that a BMD value <0.065 gm/cm³ was associated with a 7‐fold higher risk of fracture than a BMD value ≥0.065 gm/cm³.

Conclusion

In postmenopausal women with osteoporosis induced by long‐term glucocorticoid treatment who are also receiving HRT, BMD of the lumbar spine as measured by QCT, but not DXA, is an independent predictor of vertebral fractures.

     

Bone mineral density and coronary atherosclerosis

Background

The association between low bone mineral density (BMD) and atherosclerosis is still unknown. In this study BMD assessed in patients with and without coronary artery atherosclerosis is determined by angiography.

Methods

A total number of 123 consecutive patients referred for coronary angiography were evaluated by dual X-ray absorptiometry. Obstructive CAD was diagnosed when ⩾50% of lumen was narrowed. Conventional atherosclerosis risk factors were also assessed.

Results

The mean age of the patients was 59 ± 8 years. There was frequency of 48.7% male. The prevalence of diabetes was 31.2%, hypertension 57%, dyslipoproteinaemia 51%, vitamin D deficiency 50% and history of smoking 80.8%. Coronary angiography was normal in 15 patients (12.6%) while 67 patients (55.5%) had obstructive CAD. DXA scan showed 25 patients (21%) with normal BMD, 39 patients (32.7%) with osteopenia, and 55 others (46.2%) with osteoporosis. Lower BMD results were significantly associated with older age and lower BMI but it was not associated significantly with diabetes, hypertension, lipids levels or smoking. Moreover the prevalence of obstructive CAD and minimal CAD differed between groups with normal and low bone density but this was not significant (p = 0.67 and 0.52, respectively). The mean T score comparison between patients with and without CAD was also not different.

Conclusions

In patients with and without obstructive CAD the prevalence of low BMD results are not different.     

Bone Microarchitecture in Hemodialysis Patients Assessed by HR-pQCT

Summary

Background and objectives

Dialysis patients are at high risk for low-trauma bone fracture. Bone density measurements using dual-energy x-ray absorptiometry (DXA) do not reliably differentiate between patients with and without fractures. The aim of this study was to identify differences in bone microarchitecture between patients with and without a history of fracture using high-resolution peripheral quantitative computed tomography (HR-pQCT).

Design, setting, participants, & measurements

Seventy-four prevalent hemodialysis patients were recruited for measurements of areal bone mineral density (aBMD) by DXA and bone microarchitecture by HR-pQCT. Patients with a history of trauma-related fracture were excluded. Forty healthy volunteers served as controls. Blood levels of parathyroid hormone, vitamin D, and markers of bone turnover were determined.

Results

Dialysis patients, particularly women, had markedly impaired bone microarchitecture. Patients with fractures had significantly reduced cortical and trabecular microarchitecture compared with patients without fractures. aBMD tended to be lower in patients with fractures, but differences were statistically not significant. The strongest determinant of fracture was the HR-pQCT-measured trabecular density of the tibia, which also had the highest discriminatory power to differentiate patients according to fracture status. Radial DXA had a lower discriminatory power than trabecular density.

Conclusions

Bone microarchitecture is severely impaired in dialysis patients and even more so in patients with a history of fracture. HR-pQCT can identify dialysis patients with a history of low-trauma fracture.     

定量CT测量髋关节骨密度的重复性与DXA测量的一致性

目的 探讨定量CT（QCT）髋关节骨密度（BMD）测量重复性及与双能X线骨密度测定仪（DXA）测量的一致性.方法 随机抽取28名（男10例,女18例）老年受试者（男性＞60岁,女性＞50岁）,并分别采用QCT与DXA测量髋关节骨密度.收集左侧髋关节QCT扫描CT原始数据,分别由3名操作者各测量1次,其中1名操作者在不同时间重复测量3次,用于评价QCT髋关节骨密度结果的重复性.比较QCT和DXA测量左侧髋关节骨密度结果.结果 3名不同操作者或同一操作者不同时间采用QCT测量28名受试者左侧髋关节的骨密度值之间具有很好的相关性（ICC：0.93～0.98,P＜0.01）,全髋骨密度值之间差异无统计学意义.DXA与QCT测量的股骨颈和全髋骨密度结果之间具有显著相关性（r=0.88,0.89,P＜0.01）,DXA测量的骨密度值较QCT相对应骨密度值大10.5%和9.7%（t=7.53,9.68,P＜0.01）.上述骨密度值系统误差可被校正.结论采用QCT测量髋关节BMD具有较好的重复性,其BMD值与DXA所测BMD结果具有相关性.QCT髋关节（CTXA）骨密度测量可用于骨质疏松症的诊断和疗效随访,具有临床应用前景.     

Quantitative computed tomography of the lumbar spine,not dual x-ray absorptiometry,is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy

OBJECTIVE: To determine which measurement of bone mineral density (BMD) predicts vertebral fractures in a cohort of postmenopausal women with glucocorticoid-induced osteoporosis. METHODS: We recruited 114 subjects into the study. All had osteopenia of the lumbar spine or hip, as demonstrated by dual x-ray absorptiometry (DXA), and were receiving long-term glucocorticoids and hormone replacement therapy (HRT). Measurements of BMD by DXA of the lumbar spine, hip (and subregions), and forearm (and subregions), quantitative computed tomography (QCT) of the spine and hip (n = 59), and radiographs of the thoracolumbar spine were performed on all subjects to assess prevalent vertebral fractures. Vertebral fracture prevalence, as determined by morphometry, required a >or=20% (or >or=4-mm) loss of vertebral body height. Demographic information was obtained by questionnaire. Multiple regression and classification and regression trees (CART) analyses were used to assess predictors of vertebral fracture. RESULTS: Twenty-six percent of the study subjects had prevalent fractures. BMD of the lumbar spine, total hip and hip subregions, as measured by QCT, but only the lumbar spine and total hip, as measured by DXA, were significantly associated with prevalent vertebral fractures. However, only lumbar spine BMD as measured by QCT was a significant predictor of vertebral fractures. CART analysis showed that a BMD value <0.065 gm/cm(3) was associated with a 7-fold higher risk of fracture than a BMD value >or=0.065 gm/cm(3).CONCLUSION: In postmenopausal women with osteoporosis induced by long-term glucocorticoid treatment who are also receiving HRT, BMD of the lumbar spine as measured by QCT, but not DXA, is an independent predictor of vertebral fractures.     

Once-monthly oral ibandronate improves biomechanical determinants of bone strength in women with postmenopausal osteoporosis

CONTEXT: Bone strength and fracture resistance are determined by bone mineral density (BMD) and structural, mechanical, and geometric properties of bone. DESIGN, SETTING, AND OBJECTIVES: This randomized, double-blind, placebo-controlled outpatient study evaluated effects of once-monthly oral ibandronate on hip and lumbar spine BMD and calculated strength using quantitative computed tomography (QCT) with finite element analysis (FEA) and dual-energy x-ray absorptiometry (DXA) with hip structural analysis (HSA). PARTICIPANTS: Participants were women aged 55-80 yr with BMD T-scores -2.0 or less to -5.0 or greater (n = 93). INTERVENTION: Oral ibandronate 150 mg/month (n = 47) or placebo (n = 46) was administered for 12 months. OUTCOME MEASURES: The primary end point was total hip QCT BMD change from baseline; secondary end points included other QCT BMD sites, FEA, DXA, areal BMD, and HSA. All analyses were exploratory, with post hoc P values. Results: Ibandronate increased integral total hip QCT BMD and DXA areal BMD more than placebo at 12 months (treatment differences: 2.2%, P = 0.005; 2.0%, P = 0.003). FEA-derived hip strength to density ratio and femoral, peripheral, and trabecular strength increased with ibandronate vs. placebo (treatment differences: 4.1%, P < 0.001; 5.9%, P < 0.001; 2.5%, P = 0.011; 3.5%, P = 0.003, respectively). Ibandronate improved vertebral, peripheral, and trabecular strength and anteroposterior bending stiffness vs. placebo [7.1% (P < 0.001), 7.8% (P < 0.001), 5.6% (P = 0.023), and 6.3% (P < 0.001), respectively]. HSA-estimated femoral narrow neck cross-sectional area and moment of inertia and outer diameter increased with ibandronate vs. placebo (respectively 3.6%, P = 0.003; 4.0%, P = 0.052; 2.2%, P = 0.049). CONCLUSIONS: Once-monthly oral Ibandronate for 12 months improved hip and spine BMD measured by QCT and DXA and strength estimated by FEA of QCT scans.     

Bone Density and Bone Metabolism in Patients with Inflammatory Bowel Disease

Background/Aims:

Patients with inflammatory bowel disease (IBD) are at high risk for low bone mineral density (BMD). This study aimed to evaluate BMD in IBD patients and its relationship with bone metabolism in a group of Iranian patients.

Patients and Methods:

A cross-sectional study was conducted on patients with IBD to assess BMD status and serum biochemical factors. After getting the demographic data from 200 patients, they were screened using dual-energy X-ray absorptiometry of the lumbar spine (L2–L4) and femoral neck for BMD status. Serum levels of calcium, phosphate, alkaline phosphatase (ALP), and 25-hydroxyvitamin D (25-OH vitamin D) were measured to assess the bone metabolism status.

Results:

Two hundred patients with IBD were enrolled in the study. One hundred and eighty three (91.5%) patients were identified as having ulcerative colitis (UC) and 17 (8.5%) as having Crohn''s disease (CD). Based on the lumbar and femoral neck bone mass densitometry, 148 (74.4%) patients had low BMD at either lumbar spine or femoral neck. Of these, 100 patients (50.3%) were osteopenic and 48 patients (24.1%) were osteoporotic. A 58.6% and 61% of patients with UC had low BMD in the lumbar and femoral neck, respectively. These results for those with CD were 76.5% and 70.6%, respectively. The mean of femoral neck and lumbar T-scores in patients with UC were -1.14 and -1.38, and in patients with CD were -1.24 and -1.47, respectively (P > 0.05). The mean (±SD) levels for calcium (Ca) in UC and CD were in the normal range. The mean (±SD) levels of ALP and 25-OH vitamin D in both the groups were in the normal range, and in comparison between groups (UC and CD), no significant differences were observed (P = 0.20 for ALP and P = 0.44 for 25-OH vitamin D). In the assessment of correlation between biochemical markers and BMD, an inverse correlation between lumbar T-score and ALP or 25-OH vitamin D only in patients with UC was observed.

Conclusions:

The high prevalence of low BMD in the Iranian population with IBD needs attention. The subclinical vitamin D deficiency may contribute to bone loss in IBD patients, which is more pronounced in patients with UC in this study because of the small population of patients with CD.     

Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer

Purpose

While their negative impact on bone health is well established, the effects of aromatase inhibition (AI) on Wnt inhibitors and osteoprotegerin (OPG) are unknown. The aim of the study was to investigate the effects of AI on serum levels of sclerostin, DKK-1 and OPG, as well as their associations with PINP and CTX as markers of bone turnover and bone mineral density (BMD) assessed by DXA.

Methods

We conducted a prospective longitudinal analysis of 70 postmenopausal women with hormone receptor-positive early breast cancer (BC) treated with anastrozole. All measurements were performed at baseline, 12 and 24 months of treatment. We measured the association of the investigated variables with circulating bone turnover markers, as well as with the BMD.

Results

After 24 months of AI therapy, sclerostin and OPG concentrations increased from 29.5 pmol/l (SD = 15.1) and 6.8 pmol/l (SD = 2.2) at baseline to 43.2 pmol/l (SD = 20.6) (p < 0.001) and 7.4 pmol/l (SD = 2.2) (p = 0.028), respectively. DKK-1 levels decreased from 34.3 pmol/l (SD = 13.5) at baseline to 29.7 pmol/l (SD = 12.3) at the 24-month visit (p = 0.005). Sclerostin levels significantly correlated with PTH, OPG and BMD of the lumbar spine, while DKK-1 correlated with the BMD of the femoral neck and of the total hip.

Conclusions

The observed increase in sclerostin levels indicates a central role of osteocytes in bone turnover in women with BC.     

Effects of denosumab treatment in chronic liver disease patients with osteoporosis

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

Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis

CONTEXT: Treatment of osteoporotic women with PTH increases biochemical markers of bone turnover, increases axial bone mineral density (BMD), and reduces fracture risk. OBJECTIVE: Our objective was to determine the relationship between levels of baseline turnover before PTH therapy and short-term changes in turnover during PTH therapy and subsequent changes in areal and volumetric BMD. DESIGN AND SETTING: We conducted a randomized, placebo-controlled trial at four academic centers. PATIENTS: Patients included 238 postmenopausal women with low hip or spine BMD. INTERVENTION: Subjects were randomized to sc PTH (1-84), 100 mug/d (119 women), for 1 yr. MAIN OUTCOME MEASURE: Bone turnover markers were measured in fasting blood samples collected before therapy and after 1 and 3 months. Areal and volumetric BMD at the spine and hip were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography (QCT) after 1 yr of therapy. RESULTS: Among women treated with PTH alone, the relationships between baseline turnover and 1-yr changes in dual-energy x-ray absorptiometry and QCT BMD were inconsistent. Greater 1- and 3-month increases in turnover, particularly the formation marker N-propeptide of type I collagen, were associated with greater increases in areal BMD. When volumetric hip and spine BMD were assessed by QCT, greater short-term increases in turnover were even more positively associated with 1-yr increases in BMD. Each sd increase in the 3-month change of N-propeptide of type I collagen was associated with an a 21% greater increase in QCT spine trabecular BMD. CONCLUSIONS: Greater short-term changes in turnover with PTH therapy are associated with greater 1-yr increases in spine and hip BMD among postmenopausal osteoporotic women.     

Bone loss in patients with rheumatoid arthritis: Results from a population‐based cohort of 366 patients followed up for two years

Objective

To evaluate the extent of and risk factors for bone loss in a population‐based cohort of patients with rheumatoid arthritis (RA) receiving conventional health care.

Methods

In a longitudinal study, clinical data were collected and bone mineral density (BMD) measurements were performed at baseline and after 2 years. Dual‐energy x‐ray absorptiometry was used for hip and spine BMD measurements. At baseline, patients received advice about lifestyle adjustments and calcium and vitamin D supplementation; during the followup period they were treated with antirheumatic and bone‐sparing drugs, according to clinical judgment.

Results

After a mean ± SD of 2.2 ± 0.2 years, 366 (298 women, 68 men) of the 488 patients who were examined at baseline were reexamined. At that time, 47.9% were current users of corticosteroids and 37.0% were using antiresorptive drugs (hormone replacement therapy, bisphosphonates, or calcitonin). The mean BMD reduction was −0.64% in the femoral neck, −0.77% in the total hip, and −0.29% in the spine at L2‐4. BMD was increased at all measurement sites in current users of antiresorptive drugs (0.16–1.64%) but was decreased in patients using calcium and vitamin D alone (−1.99% to −1.39%) and in patients not using any osteoporosis treatment (−1.20% to −0.43%). Current use of corticosteroids was independently associated with increased risk for BMD loss in the total hip (odds ratio [OR] 2.63, 95% confidence interval [95% CI] 1.38–5.00) and spine at L2‐4 (OR 2.70, 95% CI 1.30–5.63), whereas current use of antiresorptive drugs was associated with decreased risk for bone loss in the total hip (OR 0.43, 95% CI 0.20–0.89).

Conclusion

Results of this population‐based, 2‐year followup study indicate that adequate management of patients with RA, addressing both the rheumatic disease and osteoporosis, protects against bone loss.

     

Expression of Fibroblast Growth Factor 23, Vitamin D Receptor,and Sclerostin in Bone Tissue from Hypercalciuric Stone Formers

Background and objectives

Increased bone resorption, low bone formation, and abnormal mineralization have been described in stone formers with idiopathic hypercalciuria. It has been previously shown that the receptor activator of NF-κB ligand mediates bone resorption in idiopathic hypercalciuria (IH). The present study aimed to determine the expression of fibroblast growth factor 23 (FGF-23), vitamin D receptor (VDR), and sclerostin in bone tissue from IH stone formers.

Design, setting, participants, & measurements

Immunohistochemical analysis was performed in undecalcified bone samples previously obtained for histomorphometry from 30 transiliac bone biopsies of idiopathic hypercalciuria stone-forming patients between 1992 and 2002 and 33 healthy individuals (controls). Serum parameters were obtained from their medical records.

Results

Histomorphometry disclosed 21 IH patients with high and 9 IH patients with normal bone resorption. Importantly, eroded surfaces (ES/BS) from IH patients but not controls were significantly correlated with VDR immunostaining in osteoblasts (r=0.51; P=0.004), sclerostin immunostaining in osteocytes (r=0.41; P=0.02), and serum 1,25-dihydroxyvitamin D (r=0.55; P<0.01). Of note, both VDR and sclerostin immunostaining were significantly correlated with serum 1,25-dihydroxyvitamin D in IH patients (r=0.52; P=0.01 and r=0.53; P=0.02, respectively), although VDR and sclerostin expression did not differ between IH and controls. IH patients with high bone resorption exhibited a significantly stronger sclerostin immunostaining than IH patients with normal bone resorption. FGF-23 expression in osteocytes from IH patients did not differ from controls and was not correlated with any histomorphometric parameter.

Conclusions

These findings suggest the contribution of VDR and sclerostin, as well as 1,25-dihydroxyvitamin D, to increase bone resorption in idiopathic hypercalciuria but do not implicate FGF-23 in the bone alterations seen in these patients.     

Frequency of Low Bone Mineral Density in Saudi Patients with Inflammatory Bowel Disease

Background/Aims:

Metabolic bone disease is common in patients with inflammatory bowel disease (IBD). Our aim was to determine the frequency of bone loss among Saudi patients with IBD and possible contributing risk factors.

Settings and Design:

We retrospectively reviewed Saudi patients with IBD, between 18 and 70 years of age, who had bone mass density (BMD) determined by dual-energy X-ray absorptiometry scanning at one of three hospitals in the Kingdom of Saudi Arabia from 2001 to 2008.

Patients and Methods:

Case notes and BMDs results were carefully reviewed for demographic and clinical data. Low bone mass, osteopenia, and osteoporosis were defined according to the WHO guidelines.

Statistical Analysis Used:

Predictive factors for BMD were analyzed using group comparisons and stepwise regression analyses.

Results:

Ninety-five patients were included; 46% had Crohn''s disease (CD) and 54% had ulcerative colitis (UC). The average age was 30.9±11.6 years. Using T-scores, the frequency of osteopenia was 44.2%, and the frequency of osteoporosis was 30.5% at both lumbar spine and proximal femur. Only 25.3% of patients exhibited a BMD within the normal range. Our results revealed a positive correlation between the Z-score in both the lumbar spine and the proximal femur and body mass index (BMI) (P=0.042 and P=0.018, respectively). On regression analysis BMI, age, and calcium supplementation were found to be the most important independent predictors of BMD.

Conclusions:

Saudi patients with IBD are at an increased risk of low BMD and the frequency of decreased BMD in Saudi patients with CD and UC were similar. BMI and age were the most important independent predictors of low BMD.     

Benefits of 2 years of intense exercise on bone density, physical fitness, and blood lipids in early postmenopausal osteopenic women: results of the Erlangen Fitness Osteoporosis Prevention Study (EFOPS)

BACKGROUND: Growing evidence indicates that physical exercise can prevent at least some of the negative effects on health associated with early menopause. Here we determine the effects of intense exercise on physical fitness, bone mineral density (BMD), back pain, and blood lipids in early postmenopausal women. METHODS: The study population comprised 50 fully compliant women, with no medication or illness affecting bone metabolism, who exercised over 26 months (exercise group [EG]), and 33 women who served as a nontraining control group (CG). Two group training sessions per week and 2 home training sessions per week were performed in the EG. Both groups were individually supplemented with calcium and cholecalciferol. Physical fitness was determined by maximum strength and cardiovascular performance. Bone mineral density was measured at the lumbar spine (dual-energy x-ray absorptiometry [DXA] and quantitative computed tomography [QCT]), the proximal femur (DXA), and the forearm (DXA). In serum samples taken from a subset of the study participants, we determined bone formation (serum osteocalcin) and resorption (serum cross-links) markers as well as blood lipid levels. Vasomotor symptoms related to menopause and pain were also assessed. RESULTS: After 26 months, significant exercise effects determined as percentage changes compared with baseline were observed for physical fitness (isometric strength: trunk extensors [EG +36.5% vs CG +1.7%], trunk flexors [EG +39.3% vs CG -0.4%], and maximum oxygen consumption [EG +12.4% vs CG -2.3%]); BMD (lumbar spine [DXA L1-L4, EG +0.7% vs CG -2.3%], QCT L1-L3 trabecular region of interest [EG +0.4% vs CG -6.6%], QCT L1-L3 cortical region of interest [EG +3.1% vs CG -1.7%], and total hip [DXA, EG -0.3% vs CG -1.7%]); serum levels (total cholesterol [EG -5.0% vs CG +4.1%] and triglycerides [EG -14.2% vs CG +23.2%]); and pain indexes at the spine. CONCLUSION: General purpose exercise programs with special emphasis on bone density can significantly improve strength and endurance and reduce bone loss, back pain, and lipid levels in osteopenic women in their critical early postmenopausal years.     

The Impact of Fragility Fractures on Health-Related Quality of Life in Patients With Primary Sclerosing Cholangitis

Background:

Osteoporosis occurs frequently in patients with chronic cholestatic liver diseases, yet data are scarce regarding the prevalence of osteoporosis and fragility fractures and their impact on Health-Related Quality of Life (HRQoL) in Primary Sclerosing Cholangitis (PSC).

Objectives:

We aimed to assess Bone Mineral Density (BMD), physical activity and incidence of fragility fractures in patients with PSC. We also sought associations between prior fractures and HRQoL.

Patients and Methods:

The study was performed on 33 patients (11 females, 22 males) aged 35.3 ± 13 years. HRQoL was assessed by Short Form (SF)-36, Primary Biliary Cirrhosis (PBC)-40 and PBC-27 questionnaires. BMD was measured by densitometry in the lumbar spine and hip. Physical activity was assessed by questionnaire.

Results:

In 32% of patients, BMD measured in the hip or spine was below 1.0 Standard Deviation. A history of fragility fractures (distal forearm and ribs) was reported in six patients (18%). In SF-36 assessment, patients with fractures had lower scores in the role functioning, general health and vitality domains and Physical Component Summary (PCS) than those without fractures. Prior fractures adjusted for gender and PSC duration were associated with lower PCS and Mental Component Summary (MCS) scores. Symptoms and fatigue (assessed by PBC) and prior fractures were inversely associated with MCS (P = 0.007).

Conclusions:

In middle-aged subjects with PSC, we found a high rate of non-vertebral fractures and a moderately decreased BMD in lumbar spine and hip. Fragility fractures had an impact on physical and mental aspects of HRQoL.     

Denosumab‐mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients

Objective

Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores.

Methods

Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x‐ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months).

Results

There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and ?1.2% and ?2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores.

Conclusion

In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.

     

Vascular Calcification and Bone Mineral Density in Recurrent Kidney Stone Formers

Background and objectives

Recent epidemiologic studies have provided evidence for an association between nephrolithiasis and cardiovascular disease, although the underlying mechanism is still unclear. Vascular calcification (VC) is a strong predictor of cardiovascular morbidity and the hypothesis explored in this study is that VC is more prevalent in calcium kidney stone formers (KSFs). The aims of this study were to determine (1) whether recurrent calcium KSFs have more VC and osteoporosis compared with controls and (2) whether hypercalciuria is related to VC in KSFs.

Design, setting, participants, & measurements

This is a retrospective, matched case-control study that included KSFs attending an outpatient nephrology clinic of the Royal Free Hospital (London, UK) from 2011 to 2014. Age- and sex-matched non-stone formers were drawn from a list of potential living kidney donors from the same hospital. A total of 111 patients were investigated, of which 57 were KSFs and 54 were healthy controls. Abdominal aortic calcification (AAC) and vertebral bone mineral density (BMD) were assessed using available computed tomography (CT) imaging. The prevalence, severity, and associations of AAC and CT BMD between KSFs and non-stone formers were compared.

Results

Mean age was 47±14 years in KSFs and 47±13 in non-stone formers. Men represented 56% and 57% of KSFs and non-stone formers, respectively. The prevalence of AAC was similar in both groups (38% in KSFs versus 35% in controls, P=0.69). However, the AAC severity score (median [25th percentile, 75th percentile]) was significantly higher in KSFs compared with the control group (0 [0, 43] versus 0 [0, 10], P<0.001). In addition, the average CT BMD was significantly lower in KSFs (159±53 versus 194 ±48 Hounsfield units, P<0.001). A multivariate model adjusted for age, sex, high BP, diabetes, smoking status, and eGFR confirmed that KSFs have higher AAC scores and lower CT BMD compared with non-stone formers (P<0.001 for both). Among stone formers, the association between AAC score and hypercalciuria was not statistically significant (P=0.86).

Conclusions

This study demonstrates that patients with calcium kidney stones suffer from significantly higher degrees of aortic calcification than age- and sex-matched non-stone formers, suggesting that VC may be an underlying mechanism explaining reported associations between nephrolithiasis and cardiovascular disease. Moreover, bone demineralization is more prominent in KSFs. However, more data are needed to confirm the possibility of potentially common underlying mechanisms leading to extraosseous calcium deposition and osteoporosis in KSFs.