High osteoporotic fracture risk and CVD risk co-exist in postmenopausal women

IntroductionOsteoporosis related risk factors such as BMD have been associated with cardiovascular endpoints in previous studies but there have been no studies of integrated risk using risk factor algorithms.MethodsA sample of 358 peri- and postmenopausal women, mean age 59.3 (range 45–74) years were studied. Each individual had bone mineral density (BMD) measurements by dual energy X-ray absorptiometry. Fracture risk was assessed using the WHO FRAX algorithm and cardiovascular disease (CVD) risk using the Framingham Risk Tool.ResultsWomen with higher 10 year risk of major osteoporotic had significantly higher cardiovascular risk (4.634% vs 8.36%, p = 0.001). In multiple regression analysis, 5-year CVD risk was significantly associated with the 10-year risk of having major osteoporotic (β = 0.095, p = 0.001) and hip (β = 0.055, p = 0.001) fracture. Women with the highest CVD risk were 5.4 times more likely to have higher risk of major osteoporotic fracture.ConclusionsFracture risk, determined by using a multiple risk factor algorithm such as FRAX, was positively associated with higher cardiovascular risk determined by using the Framingham Risk Tool. Awareness regarding these concurrent risk factors needs to be raised so that appropriate risk reduction can be implemented.     

A United Kingdom perspective on the relationship between body mass index (BMI) and bone health: A cross sectional analysis of data from the Nottingham Fracture Liaison Service

ObjectivesThis study examines the relationship between high BMI, a diagnosis of osteoporosis and low trauma fractures.MethodThis is a cross sectional analysis using data collected from the Nottingham Fracture Liaison Service. A total of 4288 participants with a low trauma fracture from 1 January 2007 to 31 August 2012 were analysed. Logistic regression adjusted for potential confounders was used investigate osteoporosis and BMI. Fracture types were compared between those who were obese and non-obese.ResultsA total of 30% (1285) were obese. Prevalence of osteoporosis was 13.4%, 24.9%, and 40.4% in the obese, overweight and normal category respectively. Being obese has an odds ratio of 0.23 (95% CI 0.19–0.28, p < 0.01) of having osteoporosis compared to a normal BMI category. When variable BMI cut offs were used (BMI 25, 30 and 35) to calculate the positive predictive value of patients not having osteoporosis, it was 80.5%, 86.3% and 88.3%. Examining fracture types, obese patients when compared with the non-obese category, were more likely to fracture their ankle (OR 1.48, p < 0.01) and upper arm (OR 1.48, p < 0.001), but were less likely to fracture their wrist (OR 0.65, p < 0.001). In the elderly (> 70 years), obesity no longer influenced ankle or wrist fractures but there is an increased risk of upper arm fractures (OR 1.46, p = 0.005).ConclusionHigher BMD in obesity is not protective against fractures as there are a significant number of fractures in this group which may be due to body habitus, mechanism of injury and the effect of adiposity on bone. A low trauma osteoporotic fracture will need to be redefined in light of these findings.     

Prevalence and risk factors of osteoporosis in Korea: A community-based cohort study with lumbar spine and hip bone mineral density

PurposeTo investigate bone mineral density (BMD) profiles, osteoporosis prevalence and risk factors in a community-based cohort in Korea.MethodsThe present study is a cross-sectional study. The study population consisted of 1,547 men and 1991 women aged 40 years and older with BMD measurements using central dual energy X-ray absorptiometry from a prospective community-based cohort. The data were compared with other ethnic groups. Risk factors related to osteoporosis were analyzed.ResultsCrude prevalence of osteoporosis in the whole subjects (40–79 years old) was 13.1% for men and 24.3% for women by WHO criteria, at any site among lumbar spine, femoral neck or total hip. Standardized prevalence of osteoporosis between age of 50 and 79 at lumbar spine, femoral neck and total hip was 12.9%, 1.3% and 0.7% in men and 24.0%, 5.7% and 5.6% in women, respectively. The mean BMD of studied female subjects after age of 50 was not significantly different from that of Chinese but significantly lower than that of Japanese, non-Hispanic whites, non-Hispanic blacks and Mexican Americans. Risk of osteoporosis was significantly associated with the presence of past fracture history (OR, 1.45; 95% CI, 1.08–1.94), smoking ≥ 1 pack/day (OR, 1.63; 95% CI, 1.01–2.62), menarche after age of 16 (OR, 1.46; 95% CI, 1.14–1.87), last delivery after age of 30 (OR, 1.58; 95% CI, 1.20–2.09), more than three offspring (OR, 1.42; 95% CI, 1.07–1.89), post-menopause status (OR, 7.32; 95% CI, 3.05–17.6), more than 17 years since menopause (OR, 1.53; 95% CI, 1.10–2.14), regular exercise of two to three times per week (OR, 0.40; 95% CI, 0.18–0.89), monthly income above 500,000 won per household (OR, 0.64; 95% CI, 0.45–0.92), college graduate (OR, 0.29; 95% CI, 0.13–0.63) and calcium intake ≥ 627.5 mg/day (OR, 0.65; 95% CI, 0.43–0.98) after adjusting for age and BMI.ConclusionThe BMD and osteoporosis prevalence of Koreans are presented. Risk of osteoporosis was significantly associated with fracture history, smoking, reproductive history, regular exercise, income level, education background and calcium intake.     

Intracranial pressure monitoring in severe traumatic brain injuries: a closer look at level 1 trauma centers in the United States

IntroductionThe Brain Trauma Foundation (BTF) recently updated recommendations for intracranial pressure (ICP) monitoring in severe traumatic brain injury (TBI). The effect of ICP monitoring on outcomes is controversial, and compliance with BTF guidelines is variable. The purpose of this study was to assess both compliance and outcomes at level I trauma centers.Materials and methodsThe American College of Surgeons Trauma Quality Improvement Program database was queried for all patients admitted to level I trauma centers with isolated blunt severe TBI (AIS > 3, GCS < 9) who met criteria for ICP monitoring. Patients who had severe extracranial injuries, craniectomy, or death in the first 24 h were excluded. Comparison between groups with and without ICP monitoring was made, analyzing demographics, comorbidities, mechanism of injury, head Abbreviated Injury Scale (AIS), vital signs on admission, head CT scan findings. Outcomes included in-hospital mortality, mechanical ventilation days, intensive care unit (ICU) length of stay, hospital length of stay, systemic complications, and functional independence at discharge. Multivariable analysis was used to identify independent risk factors for each of the outcomes.ResultsOverall, 4880 patients were included. ICP monitoring was used in 529 patients (10.8%). Stepwise logistic regression analysis identified ICP monitor placement as an independent risk factor for mortality (OR 1.63; 95% CI 1.28–2.07; p < 0.001), mechanical ventilation (OR 5.74 95% CI 4.42–7.46; p < 0.001), ICU length of stay (OR 4.03; 95% CI 2.94–5.52; p < 0.001), systemic complications (OR 2.78; 95% CI 2.29–3.37; p < 0.001), and decreased functional independence at discharge (OR 1.71 95% CI 1.29–2.26; p < 0.001). Subgroup analysis of patients with head AIS 3, 4, and 5 confirmed that ICP monitors remained an independent risk factor for mortality in both head AIS 4 and 5.ConclusionsCompliance with BTF guidelines for ICP monitoring is low, even at level I trauma centers. In this study, ICP monitoring was associated with poor outcomes, and was found to be an independent risk factor for mortality. Further studies are needed to determine the optimal role of ICP monitoring in the management of severe TBI.     

Associations between amino acids and bone mineral density in men with idiopathic osteoporosis

Idiopathic osteoporosis in middle-aged men is characterized by low-level bone formation. Inhibited anabolism may be involved in the pathogenesis of the disease and amino acids may be of importance. In the present study fasting amino acid profiles in plasma and erythrocytes were determined in 22 male idiopathic osteoporosis (MIO) patients and in 20 age-matched healthy men and associated with bone mineral density, bone histomorphometry and hormones.The osteoporotic patients had normal plasma essential amino acids but increased non-essential amino acids (p = 0.001), particularly glutamine and glycine. The ratio essential/non-essential amino acids, an index of protein nutritional status, was decreased in the MIO patients (0.59 (0.04) μmol/l, mean (SD)), compared to controls (0.66 (0.05), p = 0.001).In the MIO patients, the ratio essential/non-essential plasma amino acids (r = 0.60, p = 0.003) was positively correlated with lumbar spine bone mineral density.The erythrocyte amino acids represent a large proportion of the free amino acids in blood. A novel finding was the lower levels of erythrocyte tryptophan in MIO (12 (2) μmol/l) compared to controls (16 (3), p = 0.001) and decreased erythrocyte/plasma ratio (0.28 (0.07) vs. 0.33, (0.06), p < 0.01), suggesting an altered amino acid transport of tryptophan between plasma and erythrocytes. In the combined group of MIO and control men (n = 42), bone mineral density was positively correlated with erythrocyte tryptophan in both the lumbar spine (r = 0.45, p = 0.003) and femoral neck (r = 0.56, p < 0.001). The bone histomorphometric variables wall thickness, trabecular thickness and mineral apposition rate were all positively associated with erythrocyte tryptophan levels in the MIO patients.In the combined group of MIO and controls, a multiple regression analysis showed that erythrocyte tryptophan could explain 22% of the variation of lumbar spine and 30% of the variation in femoral neck bone mineral density.We conclude that men with idiopathic osteoporosis have changes in free amino acid profiles which indicate their altered utilization. The correlations between tryptophan and bone mineral density and bone histomorphometry suggest a link between tryptophan and osteoblast function which may be important for bone health.     

Vertebral fracture risk factors in postmenopausal women over 50 in Valencia,Spain. A population-based cross-sectional study

PurposeThis study aims to estimate the prevalence of risk factors for osteoporotic vertebral fracture and analyze the possible associations between these factors and the presence of densitometric osteoporosis and prevalent morphometric vertebral fracture.MethodsData from a population-based cross-sectional sample of 804 postmenopausal women over the age of 50 years old living in the city of Valencia (Spain) were used. The women were interviewed to identify the prevalence of osteoporotic fracture risk factors and underwent a densitometry and a dorsolumbar spine X-ray.ResultsThe most prevalent risk factors were densitometric osteoporosis (31.7%), history of parental hip fracture (19.4%), hypoestrogenism (19%), and body mass index (BMI) ≥ 30 kg/m² (35.2%). After adjusting for all covariables, densitometric osteoporosis was associated with increased age [odds ratio (OR)_{65–69 years}: 2.84, 95% confidence interval (CI): 1.75–4.61; OR_{70–74 years}: 4.01, 95% CI: 2.47–6.52; OR_75 + years: 5.96, 95% CI: 3.27–10.87] and inversely associated with high BMI (OR_25.0–29.9: 0.51, 95% CI: 0.34–0.76; OR_≥ 30: 0.30, 95% CI: 0.19–0.46). Morphometric vertebral fracture was associated with age (OR_{65–69 years}: 2.04, 95% CI: 1.03–4.05; OR_{70–74 years}: 4.05, 95% CI: 2.11–7.77; OR_75 + years: 8.43, 95% CI: 3.97–17.93), poor educational level (OR: 1.70, 95% CI: 1.06–2.72) and with densitometric osteoporosis and BMI ≥ 30 kg/m² (OR: 3.35, 95% CI: 1.85–6.07).ConclusionsThe most prevalent osteoporotic fracture risk factors were having a high BMI and the presence of densitometric osteoporosis. A higher risk of morphometric vertebral fracture in women with both low bone mineral density and high BMI was found. This association, if confirmed, has important implications for clinical practice and fracture risk tools. We also found a higher risk in women with a poor educational level. More attention should be addressed to these populations in order to control modifiable risk factors.     

Higher prevalence of morphometric vertebral fractures in patients with recent coronary events independently of BMD measurements

Cardiovascular disease and osteoporosis are important causes of morbi-mortality in the elderly and may be mutually related. Low bone mineral density (BMD) may be associated with increased risk of cardiovascular events. We investigated the prevalence of low bone mass and fractures in metabolic syndrome patients with acute coronary events. A case–control study was conducted with 150 individuals (30–80 years-old) with metabolic syndrome. Seventy-one patients had had an acute coronary syndrome episode in the last 6 months (cases) and the remaining 79 had no coronary event (controls). Cases and controls were matched for gender, BMI and age. DXA measurements and body composition were performed while spine radiographs surveyed for vertebral fractures and vascular calcification. Biochemical bone and metabolic parameters were measured in all patients. No statistically significant difference in BMD and the prevalence of osteopenia, osteoporosis and non-vertebral fractures was observed between cases and controls. The prevalence of vertebral fractures and all fractures was higher in the cases (14.1 versus 1.3%, p = 0.003 and 22.5versus7.6%, p = 0.010, respectively). Male gender (OR = 0.22 95% CI 0.58 to 0.83, p = 0.026) and daily intake of more than 3 portions of dairy products (OR = 0.19 95% CI 0.49 to 0.75, p = 0.017) were associated with lower prevalence of fractures. Cases had higher risk for fractures (OR = 4.97, 95% CI 1.17 to 30.30, p = 0.031). Bone mass and body composition parameters were not associated with cardiovascular risk factors or bone mineral metabolism. Patients with fragility fractures had higher OPG serum levels than those without fractures (p < 0.001). Our findings demonstrated that patients with recent coronary events have a higher prevalence of vertebral fractures independently of BMD.     

Rheumatoid arthritis risk in periodontitis patients: A systematic review and meta-analysis

ObjectiveMany clinical studies have been carried out to investigate the relationship between periodontitis and rheumatoid arthritis (RA). Owing to limited evidence and inconsistent findings among these studies, it is unclear whether periodontitis would increase the risk for RA. This meta-analysis was performed to evaluate whether periodontitis represents a risk factor for RA.MethodsPubMed, Cochrane Library, Embase, Web of Science, and Wanfang were searched for eligible studies that compared periodontitis patients with controls. A pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association between periodontitis and RA.ResultsThirteen studies including a total of 706611 periodontitis patients and 349983 control subjects were included. The pooled OR of RA risk between periodontitis and controls was (OR: 1.69; 95% CI: 1.31–2.17; P < 0.0001), indicating that the patients in periodontitis group had a 69% greater risk for RA than people in control group. When stratified by disease type, the pooled results showed periodontitis represents a risk factor for incident RA (OR = 1.70, 95%CI: 0.75–3.85, P < 0.001) and mixed RA (OR = 1.61, 95%CI: 1.26–2.06; P < 0.001). When stratified by disease duration, the pooled results showed periodontitis represents a risk factor for RA disease duration > 5 years (OR = 2.88, 95%CI: 0.66–12.62, P = 0.018), disease duration < 5 years (OR = 2.59, 95%CI: 0.83–8.11, P < 0.001), mixed disease duration (OR = 1.53; 95%CI: 1.05–2.22, P < 0.001).ConclusionOur meta-analysis revealed an increased risk of RA in patients with periodontitis compared to healthy controls. Moreover, when stratified by disease type, there was a higher risk between incident RA and periodontitis. When stratified by disease duration, the patients with periodontitis might be more closely associated with the RA patients with disease duration >5 years.     

Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy

BackgroundPostmenopausal women with osteoporosis/osteopenia are at increased risk of fracture. Aromatase inhibitors further increase bone loss in these patients. This study evaluates whether zoledronic acid prevents the bone loss expected when these patients initiate letrozole.Patients and methodsPostmenopausal women with estrogen and/or progesterone receptor-positive breast cancer and a bone mineral density (BMD) T-score <?2.0 were given letrozole 2.5 mg/vitamin D 400 international units daily, calcium 500 mg twice daily, and 4 mg zoledronic acid every 6 months. The BMD was assessed at baseline and 1 year. The primary endpoint was the mean change in lumbar spine (LS) BMD at 1 year.ResultsForty-six patients completed 1 year of treatment. LS BMD increased by 2.66% (p = 0.01), femoral neck (FN) by 4.81% (p = 0.01), and any measured endpoint by 4.55% (p = 0.0052).ConclusionsZoledronic acid prevents bone loss in postmenopausal women with osteoporosis/osteopenia starting letrozole and is associated with improvements in BMD.     

Duration of breastfeeding as a risk factor for vertebral fractures

PurposeAmong the risk factors for osteoporosis and fractures, gynecological history (fertile period, parity and breastfeeding) play an important part. Changes in calcium metabolism to enable an adequate mineral transfer to the milk have a prominent role in bone loss during breastfeeding. Data on the influence of breastfeeding in postmenopausal osteoporosis are inconsistent. The aim of the present study was to identify any association between duration of breastfeeding and vertebral fractures in postmenopausal women.MethodsAll patients underwent the following tests: bone mineral density measurements of the lumbar spine (L1–L4) and the total and femoral neck using dual-energy X-ray absorptiometry and antero-posterior and lateral radiography of the thoracic and lumbar spine to identify vertebral fractures.ResultsThe study involved 752 women with a mean age of 64.5 ± 9.3; 23% of them reported vertebral osteoporotic fractures. The women with vertebral fractures had breastfed for longer periods (11.8 ± 12.9 vs. 9.3 ± 11.2 months, p = 0.03) and had more pregnancies (2.6 ± 2.2 vs. 2.2 ± 1.3, p = 0.002). Breastfeeding for more than 18 months was associated with a two-fold risk of developing vertebral fractures (OR 2.12, 95% CI 1.14–5.38, p = 0.04), particularly in those without current or past use of drugs positively affecting bone.ConclusionsOur study showed an association between long periods of breastfeeding and vertebral fractures, supporting a role for lengthy lactation as a risk factor for osteoporotic fractures after menopause. Bearing in mind all the benefits of breastfeeding, this finding suggests the importance of an adequate calcium and vitamin D intake during pregnancy and breastfeeding, with the aid of dietary supplements if necessary.     

Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol

PurposeTo elucidate incidence and risk factors of bone mineral density and fracture risk in children with Acute Lymphoblastic Leukemia (ALL).MethodsProspectively, cumulative fracture incidence, calculated from diagnosis until one year after cessation of treatment, was assessed in 672 patients. This fracture incidence was compared between subgroups of treatment stratification and age subgroups (Log-Rank test). Serial measurements of bone mineral density of the lumbar spine (BMD_LS) were performed in 399 ALL patients using dual energy X-ray absorptiometry. We evaluated risk factors for a low BMD (multivariate regression analysis). Osteoporosis was defined as a BMD_LS ≤ − 2 SDS combined with clinical significant fractures.ResultsThe 3-year cumulative fracture incidence was 17.8%. At diagnosis, mean BMD_LS of ALL patients was lower than of healthy peers (mean BMD_LS = − 1.10 SDS, P < 0.001), and remained lower during/after treatment (8 months: BMD_LS = − 1.10 SDS, P < 0.001; 24 months: BMD_LS = − 1.27 SDS, P < 0.001; 36 months: BMD_LS = − 0.95 SDS, P < 0.001). Younger age, lower weight and B-cell-immunophenotype were associated with a lower BMD_LS at diagnosis. After correction for weight, height, gender and immunophenotype, stratification to the high risk (HR)-protocol arm and older age lead to a larger decline of BMD_LS (HR group: β = − 0.52, P < 0.01; age: β = − 0.16, P < 0.001). Cumulative fracture incidences were not different between ALL risk groups and age groups. Patients with fractures had a lower BMD_LS during treatment than those without fractures. Treatment-related bone loss was similar in patients with and without fractures (respectively: ΔBMD_LS = − 0.36 SDS and ΔBMD_LS = − 0.12 SDS; interaction group time, P = 0.30). Twenty of the 399 patients (5%) met the criteria of osteoporosis.ConclusionLow values of BMD_LS at diagnosis and during treatment, rather than the treatment-related decline of BMD_LS, determine the increased fracture risk of 17.8% in children with ALL.     

A population-based five-year study on the risk of stroke in patients with osteoporosis in Taiwan

ObjectivesOsteoporosis and stroke are common diseases in elder patients. The relationship between these two diseases is unclear. This study was intended to estimate the risk of stroke among elder persons aged ≥ 50 years within five years of being diagnosed with osteoporosis.MethodsWe retrieved data from the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan to perform a nationwide population-based study. There were 2580 patients with osteoporosis aged 50 years of age and older in the study cohort. All of them had at least 2 ambulatory care claims or at least 1 inpatient service claim. Each osteoporotic patient was matched to 5 non-osteoporotic patients based on gender, age, and the index year. Subjects in both groups were followed up for five years. Risk of developing stroke and 5-year stroke-free survival rates were evaluated.ResultsThe risk of developing stroke was 1.24 times higher in osteoporotic patients within a 5-year follow-up period compared to an age- and gender-matched cohort without osteoporosis (95% confidence interval = 1.11–1.39; p < 0.001). Patients with osteoporosis also had a significantly lower 5-year stroke-free survival rate.ConclusionsOur results indicated that patients with osteoporosis history had higher risk for development of stroke.     

The impact of osteoporosis and vertebral compression fractures on mortality and association with pulmonary function in COPD: A meta-analysis

ObjectiveOsteoporosis is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and most commonly presents as a vertebral compression fracture (VCF). Our objective was to quantify the effect of osteoporosis and VCFs on the mortality and pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC), of patients with COPD.MethodsA PubMed/Medline search was conducted using the search terms “chronic obstructive pulmonary disease”, “osteoporosis” and “vertebral compression fracture”. Meta-analyses were conducted to evaluate the differences in mortality and PFTs between patients with COPD with and without osteoporosis or VCFs, according to PRISMA guidelines. PROSPERO registration: CRD42019120335.ResultsOf the 896 abstracts identified, 27 studies describing 7662 patients with COPD of which 1883 (24.6%) had osteoporosis or VCFs, were included. Random effects model analysis demonstrated that patients with COPD and osteoporosis or VCFs had an increased OR for mortality of 2.40 (95% CI: 1.24; 4.64, I² = 89%, P < 0.01), decreased FEV₁/FVC with a mean difference of ?4.80% (95% CI: ?6.69; ?2.90, I² = 83%, P < 0.01) and decreased FEV₁, with a mean difference of ?4.91% (95% CI: ?6.51; ?3.31, I² = 95%, P < 0.01) and ?0.41 L (95% CI: ?0.59; ?0.24, I² = 97%, P < 0.01), compared to control subjects. Apart from FEV₁ (liters) in subgroup 1 (P = 0.06), all subgroup analyses found significant differences between groups, as did sensitivity analysis of low risk of bias studies.ConclusionOsteoporosis and VCFs are associated with a significant reduction in survival and pulmonary function among patients with COPD.     

Calcaneous quantitative ultrasound measurements predicts vertebral fractures in idiopathic male osteoporosis

ObjectivesThe aim of this study was to identify the differences in ultrasound bone variables (QUS) and to test the ability to discriminate male patients with and without vertebral fractures.MethodsWe therefore measured broadband ultrasound attenuation (BUA) and speed of sound (SOS) matched for bone mineral density (BMD) and vertebral deformity in idiopathic male osteoporosis.ResultsOne hundred and seventeen men (age 56.6 range 27–78) were divided into three groups (osteoporosis n = 25, osteopenia n = 58 and age-matched control n = 34) according to BMD T-score by WHO criteria. We found 66 patients (56%) with at least one vertebral deformity during the study. BMD and BUA did not differ, while SOS was lower in osteoporosis (p < 0.001) and control group (p < 0.001) between the patients with and without vertebral compression. Strong positive correlation was demonstrated between BUA and BMD (lumbar spine r = 0.44, p < 0.001, femoral neck r = 0.56, p < 0.001, radius r = 0.40, p < 0.001), while similar association between SOS and BMD values was not shown. There was no relationship between the BUA and vertebral fracture risk (Odds ratio: 1.14 95% CI: 0.80–1.61). However, the relative risk of vertebral fracture by SOS was 1.56 (95% CI: 1.08–2.62). Adjusting for age and BMI the risk of vertebral fracture did not change (odds ratio for SOS 1.50 95% CI: 1.02–2.22). After adjustment for BMD SOS was still associated with fracture risk at all measured sites (odds ratio: 1.43, 95% CI: 1.02–2.22; 1.41, 95% CI: 1.02–2.17 and 1.32, 95% CI: 1.02–2.0).ConclusionOur results suggest that BUA values are more closely related to density and structure while SOS values are able to predict fractures.     

Dual-Energy X-Ray Absorptiometry and Evaluation of the Osteoporosis Self-Assessment Tool in Men With Rheumatoid Arthritis

Males with rheumatoid arthritis (RA) are at risk for osteoporosis but infrequently undergo dual-energy X-ray absorptiometry (DXA). We examined the frequency of DXA in males enrolled in the Veterans Affairs Rheumatoid Arthritis Registry. The Osteoporosis Self-Assessment Tool (OST) index, a formula using age and weight, was calculated for all subjects. DXA was performed on 282 (35.5%) of the males who were younger (p < 0.01), had lower mean OST index score (p < 0.05), and were more likely to have been prescribed prednisone (p < 0.01) than subjects without DXA. Low bone mass (T-score < ?1) was present in 73% of subjects with DXA; 37% of subjects with low-risk OST index scores had normal bone mineral density (BMD) compared with 5.6% of those with high-risk OST index scores (p < 0.01). There was a significant but modest correlation between BMD and the OST index (r = 0.17, p < 0.01). No OST score had a sensitivity and specificity of more than 80%. Association between OST index and BMD was strongest in non-Hispanic whites, subjects older than 60 yr, and smokers. DXA was underutilized in males with RA. The OST index correlated with low bone mass but could not reliably predict osteoporosis in this population.     

High prevalence of vitamin D deficiency among middle-aged and elderly individuals in northwestern China: Its relationship to osteoporosis and lifestyle factors

PurposeVitamin D deficiency has reached epidemic proportions; this deficiency has been associated with osteoporosis and certain lifestyle factors in adults. This relationship is not well documented among the Lanzhou population in northwest China. This study sought to determine the prevalence of vitamin D deficiency and its risk factors in addition to its relationship with osteoporosis in a Chinese population living in Lanzhou.MethodsThis cross-sectional study involved 2942 men and 7158 women aged 40–75 years who were randomly selected from 3 communities in the Lanzhou urban district and examined medically. Levels of 25-hydroxy-vitamin D [25(OH)D] and other parameters were measured according to detailed inclusion criteria. Vitamin D deficiency was defined as serum 25(OH)D levels below 20 ng/mL. Calcaneus bone mineral density (BMD) was measured by quantitative ultrasound (QUS).ResultsThe prevalence of vitamin D deficiency (25(OH)D levels < 20 ng/mL) was present in 75.2% of the entire study population. Vitamin D deficiency was more prevalent in women (79.7%) than in men (64%; P < 0.001). Multiple logistic regression analysis revealed that the significant predictors of vitamin D deficiency included coronary heart disease (CHD), obesity, dyslipidemia, older age, female sex, and smoking (all P < 0.05), whereas tea intake, moderate physical activity, milk intake, vitamin D supplementation and sun exposure were protective (all P < 0.05). No significant difference in calcaneus BMD measured by QUS was noted between subjects with < 20 ng/mL and ≥ 20 ng/mL vitamin D levels (0.53 ± 0.13 vs. 0.54 ± 0.13; P = 0.089). The risk of having osteoporosis did not increase when vitamin D levels decreased from ≥ 20 ng/mL to < 20 ng/mL after multiple adjustments (OR = 1.00; 95% CI 0.85–1.16; P = 0.357).ConclusionsVitamin D deficiency is prevalent in the middle-aged and elderly northwestern Chinese population and is largely attributed to CHD, obesity, dyslipidemia, older age, female sex, and smoking. Reduced 25(OH)D levels are not associated with an increased osteoporosis risk.     

TBS and BMD at the end of AI-therapy: A prospective study of the B-ABLE cohort

IntroductionPatients with breast cancer under aromatase inhibitor (AI) treatment often develop osteoporosis and their average bone loss rate is twice that of natural reduction during menopause, increasing fracture risk. As the current diagnostic technique based on bone mineral density (BMD) provides no information on bone quality, the Trabecular Bone Score (TBS) has been proposed to reflect bone microarchitecture status. The present study was designed to assess prospective changes in TBS and lumbar spine (LS) BMD in postmenopausal women with breast cancer at completion of AI treatment.MethodsB-ABLE is a prospective cohort of 735 women with breast cancer treated with AIs according to American Society of Clinical Oncology recommendations: 5 years of AI starting within 6 weeks post-surgery or 1 month after the last cycle of chemotherapy (5y-AI group), or switching to an AI to complete 5-year therapy after 2–3 years of tamoxifen (pTMX-AI group). Patients with osteoporosis were treated with oral bisphosphonates (BP). TBS and LS-BMD changes at completion of AI therapy were evaluated by Student t-test for paired samples. Pearson correlation coefficients were computed for correlations between LS-BMD and TBS.ResultsAI treatment was completed by 277 women. Of these, 70 (25.3%) were allocated to BP therapy. The non-BP-treated patients (74.7%) showed significant decreases in TBS (− 2.94% in pTMX-AI and − 2.93% in 5y-AI groups) and in LS-BMD (− 4.14% in pTMX-AI and − 2.28% in 5y-AI groups) at the end of AI treatment. In BP-treated patients, TBS remained stable at the end of AI treatment, whereas LS-BMD showed significant increases (+ 2.30% in pTMX-AI and + 5.33% in 5y-AI groups). Moderate associations between TBS and LS-BMD values at baseline and at the end of AI treatment (r = 0.4; P < 0.001) were observed. At the end of treatment, changes in spine BMD and TBS were weakly correlated (r = 0.1, P < 0.01).ConclusionsAI therapy induces significant decreases in TBS, comparable to BMD loss. BP-treated patients maintained TBS values, whereas BMD increased. AI treatment leads to deterioration of bone microarchitecture, which seems to be attenuated by BP therapy.     

Copy number variation of the APC gene is associated with regulation of bone mineral density

IntroductionGenetic studies of osteoporosis have commonly examined SNPs in candidate genes or whole genome analyses, but insertions and deletions of DNA, collectively called copy number variations (CNVs), also comprise a large amount of the genetic variability between individuals. Previously, SNPs in the APC gene have been strongly associated with femoral neck and lumbar spine volumetric bone mineral density in older men. In addition, familial adenomatous polyposis patients carrying heterozygous mutations in the APC gene have been shown to have significantly higher mean bone mineral density than age- and sex-matched controls suggesting the importance of this gene in regulating bone mineral density. We examined CNV within the APC gene region to test for association with bone mineral density.MethodsDNA was extracted from venous blood, genotyped using the Human Hap610 arrays and CNV determined from the fluorescence intensity data in 2070 Caucasian men and women aged 47.0 ± 13.0 (mean ± SD) years, to assess the effects of the CNV on bone mineral density at the forearm, spine and total hip sites.ResultsData for covariate adjusted bone mineral density from subjects grouped by APC CNV genotype showed significant difference (P = 0.02–0.002). Subjects with a single copy loss of APC had a 7.95%, 13.10% and 13.36% increase in bone mineral density at the forearm, spine and total hip sites respectively, compared to subjects with two copies of the APC gene.ConclusionsThese data support previous findings of APC regulating bone mineral density and demonstrate that a novel CNV of the APC gene is significantly associated with bone mineral density in Caucasian men and women.     

Relationship between vitamin D deficiency and bone fragility in sickle cell disease: A cohort study of 56 adults

BackgroundRecent studies suggest that patients with sickle cell disease (SCD) have profound vitamin D (VD) deficiency. Limited data exist on the effect of VD deficiency on bone fragility in these patients.ObjectivesTo assess the prevalence of VD deficiency in adults with SCD and its consequences on bone metabolism and fragility.MethodsThis prospective study included 56 SCD adult patients (mean age 29.8 ± 9.5 years), in a clinically steady state. Clinical and laboratory data were recorded. Bone mineral density (BMD) was measured using dual X-ray absorptiometry. Fracture history, BMD, avascular osteonecrosis, H-shaped vertebra and markers of mineral metabolism were compared between two groups of patients presenting very low (≤ 6 ng/mL, n = 26) (group 1) and low (> 6 ng/mL, n = 26) (group 2) 25(OH)D concentration, respectively.ResultsMedian 25(OH)D concentration was 6 ng/mL. VD deficiency (25(OH)D < 10 ng/mL) was found in 42 out of 56 patients (75%) and secondary hyperparathyroidism in 40 (71.4%). History of fracture was documented in 17 patients (30.3%), osteopenia and/or osteoporosis in 39.6% of patients. Overall, patients of group 1 were more likely to have sustained a fracture (42.8%) compared to patients of group 2 (17.8%) (p = 0.04). These patients had also lower body mass index and significantly higher parathyroid hormone, C-terminal telopeptides of type I-collagen and bone-specific alkaline phosphatase serum levels. There was no difference between group for BMD, avascular osteonecrosis history, H-shaped vertebra, and disease severity markers.ConclusionThis study suggests that VD deficiency is a key feature in SCD-bone disease. It is highly prevalent and associated with hyperparathyroidism, bone resorption markers, and history of fracture. The optimal supplementation regimen remains to be determined.     

Consequences of spinal ankylosis on bone trabecular fragility assessed on CT scans in patients with ankylosing spondylitis. A retrospective study

IntroductionAnkylosing spondylitis (AS) patients seems to be at risk of osteoporosis but bone screening is not often performed. The objective was to evaluate the effect of vertebral ankylosis on scanographic bone attenuation coefficient (SBAC) on lumbar vertebrae in AS patients.MethodsThis study included AS patients fulfilling New York criteria who underwent both thoraco-abdomino-pelvic computed tomography and X-rays during routine follow-up. The modified stoke ankylosing spondylitis spinal score (mSASSS) was scored on X-rays, and the presence of at least one syndesmophyte (mSASSS ≥ 2) defined mSASSS+ patients. Ankylosis of a lumbar vertebra was defined by the presence of bone bridges to its two adjacent vertebrae. The SBAC was measured from L1 to L5, and the fracture threshold was set at SBAC ≤ 145 HU.ResultsA total of 73 AS patients were included (mean age: 60.3 [±10.7] years, 65 men [89%]). Sixty patients (82.2%) were mSASSS+; 13 patients (17.8%) presented ankylosis of at least one lumbar vertebra. The SBAC of each lumbar vertebra was not significantly different between mSASSS− and mSASSS+ patients. The SBAC was lower for patients with at least one bone bridge than for patients without (P < 0.05). Patients with lumbar vertebral ankylosis had a higher risk of presenting an SBAC ≤ 145 HU (OR: 4.95 (95% CI: 1.1–17.4)).ConclusionThe presence of a bone bridge and complete ankylosis of lumbar vertebra were associated with a higher risk of SBAC under the fracture threshold, suggesting structural deterioration of trabecular bone in ankylosed vertebrae in AS patients.