Judith E. Adams

Association Between Vertebral Fracture and Increased Mortality in Osteoporotic Patients

Determinants of mortality were studied in a prospective study of 677 women and men with primary or secondary osteoporosis. Prevalent vertebral fractures were associated with increased mortality, but other known predictors of mortality explain a significant proportion of the excess risk.

Quantitative ultrasound of the heel and fracture risk assessment: an updated meta-analysis

SummaryMeta-analysis of prospective studies shows that quantitative ultrasound of the heel using validated devices predicts risk of different types of fracture with similar performance across different devices and in elderly men and women. These predictions are independent of the risk estimates from hip DXA measures.IntroductionClinical utilisation of heel quantitative ultrasound (QUS) depends on its power to predict clinical fractures. This is particularly important in settings that have no access to DXA-derived bone density measurements. We aimed to assess the predictive power of heel QUS for fractures using a meta-analysis approach.MethodsWe conducted an inverse variance random effects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound [SOS], stiffness index [SI], and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic and major osteoporotic fractures) were reported based on study questions.ResultsTwenty-one studies including 55,164 women and 13,742 men were included in the meta-analysis with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fracture. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43–2.00), SOS was 1.96 (95% CI 1.64–2.34), SI was 2.26 (95%CI 1.71–2.99) and QUI was 1.99 (95% CI 1.49–2.67). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Validated devices from different manufacturers predicted fracture risks with similar performance (meta-regression p valuesu2009>u20090.05 for difference of devices). QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip BMD showed a significant and independent association with fracture risk (RR/SD for BUAu2009=u20091.34 [95%CI 1.22–1.49]).ConclusionsThis study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women. Further research is needed for more widespread utilisation of the heel QUS in clinical settings across the world.

Sarcopenia and its relationship with bone mineral density in middle-aged and elderly European men.

SummaryThe aim of this study was to determine the relationship between reduced muscle mass (sarcopenia) and areal bone mineral density (BMDa) in middle-aged and elderly community-dwelling European men. Men with sarcopenia had significantly lower BMDa and were more likely to have osteoporosis compared with men without sarcopenia.IntroductionIn men, the relationship between reduced muscle mass (sarcopenia) and BMDa is unclear. This study aimed to determine this relationship in middle-aged and elderly community-dwelling men.MethodsMen aged 40–79xa0years from the Manchester (UK) and Leuven (Belgium) cohorts of the European Male Ageing Study were invited to attend for assessment including dual-energy X-ray absorptiometry, from which appendicular lean mass (aLM), fat mass (FM) and whole-body, spine and hip BMDa were determined. Relative appendicular skeletal muscle mass (RASM) was calculated as aLM/height². Muscle strength was assessed in subjects from Leuven. Sarcopenia was defined by RASM at <7.26xa0kg/m² and by the recent definition of the European Working Group on Sarcopenia in Older People (RASM at <7.26xa0kg/m2 plus low muscle function). Linear regression was used to determine the associations between aLM, FM, muscle strength and BMDa and logistic regression to determine the association between sarcopenia and osteoporosis.ResultsSix hundred seventy-nine men with a mean age of 59.6 (SDu2009=u200910.7), contributed data to the analysis; 11.9xa0% were sarcopenic by the conventional definition. After adjustment for age and centre, aLM, RASM and FM were positively associated with BMDa. Men with RASM at <7.26xa0kg/m² had significantly lower BMDa compared with those with RASM at ≥7.26xa0kg/m2. In a multivariable model, aLM was most consistently associated with BMDa. Men with sarcopenia were more likely to have osteoporosis compared with those with normal RASM (odds ratiou2009=u20093.0; 95xa0% CIu2009=u20091.6–5.8).ConclusionsSarcopenia is associated with low BMDa and osteoporosis in middle-aged and elderly men. Further studies are necessary to assess whether maintaining muscle mass contributes to prevent osteoporosis.

Clodronate Reduces Vertebral Fracture Risk in Women With Postmenopausal or Secondary Osteoporosis: Results of a Double-Blind, Placebo-Controlled 3-Year Study

The efficacy of oral clodronate 800 mg daily to reduce vertebral fractures was studied in 593 women with postmenopausal or secondary osteoporosis. The incidence of vertebral fractures was significantly reduced by 46%. The effect was not modified by the underlying cause of osteoporosis or other baseline factors including bone mineral density, QUS, weight, and smoking.

Do the Effects of Testosterone on Muscle Strength, Physical Function, Body Composition, And Quality of Life Persist Six Months after Treatment in Intermediate-Frail and Frail Elderly Men?

CONTEXTnShort-term testosterone (T) treatment in frail elderly men improves muscle mass and strength. It is unclear whether these effects can be maintained post treatment.nnnOBJECTIVEnTo assess the durability of androgen effects in frail men.nnnDESIGN AND SETTINGnSingle center, randomized, double-blind, placebo-controlled trial to investigate the effects of 6 months T (25-75 mg daily) on muscle strength, body composition, physical function, and quality of life (QoL). Participants were assessed at the end of treatment (6 months) and 6 months after treatment cessation (12 months).nnnPARTICIPANTSn274 intermediate-frail and frail elderly men aged 65-90 years with low T levels.nnnRESULTSnMean T increased from 11.1 (3.1) nmol/liter at baseline to 18.4 (3.5) nmol/liter at 6 months, then declined to 10.5 (3.7) nmol/L at 12 months, in the T-treated group. Isometric knee extension peak torque increased in the T-treated group compared with placebo to give an adjusted mean difference (95% CI) between groups of 8.1 (-0.2 to 16.5) Nm at 6 months. Lean mass increased in the T-treated group giving a difference between groups of 1.2 (0.8 to 1.7) kg at 6 months. Somatic and sexual symptoms improved during treatment. None of these differences between groups remained at 12 months. Prostate specific antigen (PSA) levels and haematocrit increased slightly during treatment but returned to baseline by 12 months.nnnCONCLUSIONnThe effects of 6-month T treatment on muscle strength, lean mass, and QoL in frail men are not maintained at 6 months post treatment.

Quantitative ultrasound in the assessment of skeletal status.

Quantitative ultrasound (QUS) is a non-invasive technique for the investigation of bone tissue in several pathologies and clinical conditions, especially in the field of osteoporosis. The versatility of the technique, its low cost and lack of ionising radiation have led to the diffusion of this method worldwide. Several studies have been conducted in the last years to investigate the potential of QUS in multiple areas with promising results; the technique has been applied in the prediction of osteoporotic fractures, in monitoring therapies, in the investigation of secondary osteoporosis, in paediatrics, neonatology and genetics. Our review article gives an overview of the most relevant developments in the field of quantitative ultrasound, both in clinical and in experimental settings.

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: The European Male Aging Study (EMAS)

CONTEXTnThere is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.nnnOBJECTIVEnThe objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.nnnDESIGN, SETTING, AND PARTICIPANTSnMen aged 40-79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.nnnMAIN OUTCOME MEASURE(S)nQUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.nnnRESULTSnA total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.nnnCONCLUSIONSnSerum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.

Effects of Testosterone on Skeletal Muscle Architecture in Intermediate-Frail and Frail Elderly Men

BACKGROUNDnTestosterone increases lean mass and may help to counter the changes in muscle architecture associated with sarcopenia. This study was designed to investigate the effects of testosterone replacement therapy on skeletal muscle architecture in intermediate-frail and frail elderly men.nnnMETHODSnA subgroup of 30 intermediate-frail and frail elderly men (65-89 years) with low to borderline-low testosterone levels were enrolled from a single-center randomized, double-blind placebo-controlled trial. Participants received either a transdermal testosterone (50 mg) or placebo gel daily for 6 months. Architecture (muscle thickness, fascicle length, and pennation angle) of the gastrocnemius medialis muscle was assessed by ultrasound imaging at baseline and after 6 months of treatment.nnnRESULTSnSerum testosterone increased from 11.6 ± 3.5 to 18.0 ± 8.1 nmol/L by 10 days after randomization in the active group (but not the placebo group) and was maintained throughout the treatment period. Testosterone treatment resulted in a preservation of muscle thickness at 6 months while it decreased in the placebo group (effect size 1.4 [95% confidence interval = 0.3-2.5; p = .015]). There was no significant effect of treatment on fascicle length (effect size 1.9 mm [95% confidence interval = -1.2 to 5.0 mm; p = .22]) or pennation angle (effect size 1.2° [95% confidence interval = -1.3 to 3.7°; p = .32]).nnnCONCLUSIONSnTestosterone replacement in intermediate-frail and frail elderly men is associated with preservation of muscle thickness. The results suggest that testosterone mitigates sarcopenia by improving muscle tissue to maintain a state of normality in aging men.

Genetic Variation in the RANKL/RANK/OPG Signaling Pathway Is Associated With Bone Turnover and Bone Mineral Density in Men

The aim of this study was to determine if single‐nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r2u2009≥u20090.8) were selected for RANKL, RANK, and OPG and their 10‐kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome‐wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population‐based study of male aging, the European Male Ageing Study (EMAS). N‐terminal propeptide of type I procollagen (PINP) and C‐terminal cross‐linked telopeptide of type I collagen (CTX‐I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total‐hip areal BMD (BMDa) was measured by dual‐energy X‐ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (βu2009=u20091.83, pu2009=u2009.004) and CTX‐I (βu2009=u200917.59, pu2009=u20094.74u2009×u200910−4), and lower lumbar spine BMDa (βu2009=u2009−0.02, pu2009=u2009.026). The minor allele of rs9594759 (C) was associated with lower PINP (βu2009=u2009−1.84, pu2009=u2009.003) and CTX‐I (βu2009=u2009−27.02, pu2009=u20096.06u2009×u200910−8) and higher ultrasound BMD at the calcaneus (βu2009=u20090.01, pu2009=u2009.037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men.

Official Positions for FRAX Bone Mineral Density and FRAX Simplification From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX

Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX® without BMD input, the use of FRAX® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX®-related issues.