Toni Rikkonen

Relationship between postmenopausal osteoporosis and the components of clinical sarcopenia

PURPOSE The aim of the study was to determine the relationship between the components of clinical sarcopenia and osteoporosis in postmenopausal women. METHODS A population-based cohort of 590 Finnish postmenopausal women (mean age 67.9; range 65-72) was selected from the Osteoporosis Fracture Prevention (OSTPRE-FPS) study in 2002. Bone mineral density (BMD) and lean tissue mass were assessed by dual X-ray absorptiometry (DXA). The study sample was divided into three categories according to the WHO BMD classification: normal, osteopenia and osteoporosis. The study sample was divided into non-sarcopenic, presarcopenic, sarcopenic and non-classified groups according to quartiles of RSMI i.e. relative skeletal muscle index (appendicular muscle mass (kg)/square of height (m)), hand grip strength (kPa) and walking speed. RESULTS In logistic regression analysis sarcopenic women had 12.9 times higher odds of having osteoporosis (p ≤ 0.001, OR=12.9; 95% CI=3.1-53.5) in comparison to non-sarcopenic women. In comparison to women in the highest grip strength quartile, women within the lowest quartile had 11.7 times higher odds of having osteoporosis (p=0.001, OR=11.7; 2.6-53.4). Sarcopenic women had 2.7 times higher odds of having fractures than their non-sarcopenic counterparts (p=0.005, OR=2.732; 1.4-5.5). Sarcopenic women had also 2.1 times higher risk of falls during the preceding 12 months compared to non-sarcopenic women (p=0.021, OR=2.1; 1.1-3.9). Adjustment for age, body mass index (BMI), physical activity and hormone therapy (HT) did not significantly alter these results. CONCLUSIONS The components of clinical sarcopenia are strongly associated with osteoporosis. Grip strength is the most significant measurement to reveal the association between sarcopenia and osteoporosis, falls and fractures.

Effect of vitamin D3 and calcium on fracture risk in 65‐ to 71‐year‐old women: A population‐based 3‐year randomized, controlled trial—the OSTPRE‐FPS

Antifracture efficacy of high‐dose vitamin D (800 IU) and calcium (1000 mg) remains controversial. To determine whether daily 800 IU of vitamin D and 1000 mg of calcium supplementation prevents fractures, we randomized 3432 women of the population‐based Osteoporosis Risk Factor and Prevention (OSTPRE) Study cohort (ages 65 to 71 years) living in the region of northern Savonia, Finland (latitude 62° to 64°N) for 3 years to receive 800 IU of cholecalciferol and 1000 mg of calcium as calcium carbonate or to a control group that did not receive placebo. The main outcome measure was incident fractures. Fracture data were collected in telephone interviews and validated. Data on 3195 women, 1586 in the intervention group and 1609 in the control group, were available for analysis. In adjusted Cox proportional hazards models, the risk of any fracture decreased in the vitamin D and calcium group by 17% [adjusted hazard ratio (aHR) = 0.83; 95% confidence interval (CI) 0.61–1.12], and the risk of any nonvertebral fracture decreased by 13% (aHR = 0.87; 95% CI 0.63–1.19). The risk of distal forearm fractures decreased by 30% (aHR = 0.70; 95% CI 0.41–1.20), and the risk of any upper extremity fractures decreased by 25% (aHR = 0.75; 95% CI 0.49–1.16), whereas the risk of lower extremity fractures remained essentially equal (aHR = 1.02; 95% CI 0.58–1.80). None of these effects reached statistical significance. In conclusion, this study did not produce statistically significant evidence that vitamin D and calcium supplementation prevents fractures in a 65‐ to 71‐year‐old general population of postmenopausal women.

Physical activity slows femoral bone loss but promotes wrist fractures in postmenopausal women: A 15-year follow-up of the OSTPRE study

Results on fracture risk among physically active persons are contradictory. The aim of this study was to investigate the long‐term association between the self‐reported physical activity (PA), the risk of fractures, and bone loss among peri‐ and postmenopausal women. The association between PA and fracture risk was examined during 15 years of follow‐up in the population‐based Osteoporosis Risk Factor and Prevention (OSTPRE) Study among 8560 women with a mean age of 52.2 years (range 47 to 56 years) at baseline. The amount and type of PA, as well as the types and mechanisms of fractures, were registered with self‐administered questionnaires at 5‐year intervals (ie, 1989, 1994, 1999, and 2004). A total of 2641 follow‐up fractures were verified in 2073 women (24.2%). The study cohort was divided into quartiles by average hours of reported PA during the whole follow‐up. Areal bone mineral density (aBMD) at the proximal femur (n = 2050) and lumbar spine (L2–L4; n = 1417) was followed at 5‐year intervals from a random stratified subsample with dual X‐ray absorptiometry (DXA). Risk of fracture was estimated by using the Cox proportional hazards model with a mean follow‐up time of 15.2 years. Weekly average time spent on leisure‐time PA was 0.4, 1.7, 3.3, and 7.0 hours from the least to the most active quartiles, respectively. The risk of wrist fracture was higher in the active quartiles (II to IV) than in the most inactive quartile (I), with hazard ratios (HRs) of 1.3 [95% confidence interval (CI) 1.05–1.57, p = .014] for the second (II), 1.2 (95% CI 1.01–1.51, p = .045) for the third (III), and 1.4 (95% CI 1.14–1.69, p = .001) for the fourth (IV) quartile, respectively. Overall, most of the fractures were reported as a result of a fall (69.0%), with a 2.1 times higher rate of wrist fractures during the winter (November to April) than during summer season. There were no significant associations of PA with any other fracture types. Bone loss at the femoral neck, trochanter, and Wards triangle was significantly associated with long‐term PA (ANCOVA p < .05), whereas no associations of bone loss and PA in lumbar spine were seen. PA is associated with a moderate rise in wrist fracture risk, which might be explained in part by a higher number of outdoor activities. Regular PA of at least 1½ hours per week does not seem to increase the risk of other fractures and might significantly decrease proximal femur bone loss among peri‐ and postmenopausal women.

Wintertime Vitamin D Supplementation Inhibits Seasonal Variation of Calcitropic Hormones and Maintains Bone Turnover in Healthy Men

Vitamin D is suggested to have a role in the coupling of bone resorption and formation. Compared with women, men are believed to have more stable bone remodeling, and thus, are considered less susceptible to the seasonal variation of calcitropic hormones. We examined whether seasonal variation exists in calcitropic hormones, bone remodeling markers, and BMD in healthy men. Furthermore, we determined which vitamin D intake is required to prevent this variation. Subjects (N = 48) were healthy white men 21–49 yr of age from the Helsinki area with a mean habitual dietary intake of vitamin D of 6.6 ± 5.1 (SD) μg/d. This was a 6‐mo double‐blinded vitamin D intervention study, in which subjects were allocated to three groups of 20 μg (800 IU), 10 μg (400 IU), or placebo. Fasting blood samplings were collected six times for analyses of serum (S‐)25(OH)D, iPTH, bone‐specific alkaline phosphatase (BALP), and TRACP. Radial volumetric BMD (vBMD) was measured at the beginning and end of the study with pQCT. Wintertime variation was noted in S‐25(OH)D, S‐PTH, and S‐TRACP (p < 0.001, p = 0.012, and p < 0.05, respectively) but not in S‐BALP or vBMD in the placebo group. Supplementation inhibited the winter elevation of PTH (p = 0.035), decreased the S‐BALP concentration (p < 0.05), but benefited cortical BMD (p = 0.09) only slightly. Healthy men are exposed to wintertime decrease in vitamin D status that impacts PTH concentration. Vitamin D supplementation improved vitamin D status and inhibited the winter elevation of PTH and also decreased BALP concentration. The ratio of TRACP to BALP shows the coupling of bone remodeling in a robust way. A stable ratio was observed among those retaining a stable PTH throughout the study. A daily intake of vitamin D in the range of 17.5–20 μg (700–800 IU) seems to be required to prevent winter seasonal increases in PTH and maintain stable bone turnover in young, healthy white men.

Multi-site bone ultrasound measurements in elderly women with and without previous hip fractures

SummaryAbout 75% of patients suffering from osteoporosis are not diagnosed. This study describes a multi-site bone ultrasound method for osteoporosis diagnostics. In comparison with axial dual energy X-ray absorptiometry (DXA), the ultrasound method showed good diagnostic performance and could discriminate fracture subjects among elderly females.IntroductionAxial DXA, the gold standard diagnostic method for osteoporosis, predicts fractures only moderately. At present, no reliable diagnostic methods are available at the primary health care level. Here, a multi-site ultrasound method is proposed for osteoporosis diagnostics.MethodsThirty elderly women were examined using the ultrasound backscatter measurements in proximal femur, proximal radius, proximal and distal tibia in vivo. First, we predicted the areal bone mineral density (BMD) at femoral neck by ultrasound measurements in tibia combined with specific subject characteristics (density index, DI) and, second, we tested the ability of ultrasound backscatter measurements at proximal femur to discriminate between individuals with previously fractured hips from those without fractures. Areal BMD was determined by axial DXA.ResultsCombined ultrasound parameters, cortical thickness at distal and proximal tibia, with age and weight of the subject, provided a significant estimate of BMDneck (r = 0.86, p < 0.001, n = 30). When inserted into FRAX (World Health Organization fracture risk assessment tool), the DI indicated the same treatment proposal as the BMDneck with 86% sensitivity and 100% specificity. The receiver operating characteristic analyses, with a combination of ultrasound parameters and patient characteristics, discriminated fracture subjects from the controls similarly as the model combining BMDneck and patient characteristics.ConclusionsFor the first time, ultrasound backscatter measurements of proximal femur were conducted in vivo. The results indicate that ultrasound parameters, combined with patient characteristics, may provide a means for osteoporosis diagnostics.

Muscle performance after the menopause

The timing of the menopause transition has remained fairly constant throughout history. It represents a milestone in female health and, after passing through it, women experience increased musculoskeletal and cardiovascular morbidity. Muscle performance is an important determinant of functional capacity and quality of life among the elderly and is also involved in the maintenance of balance. Therefore, good muscle strength can prevent fragility fractures and lessen the burden of osteoporosis. Muscle strength begins to decline during the perimenopausal years and this phenomenon seems to be partly estrogen dependent. Randomized controlled trials have indicated that hormone replacement therapy may prevent a decline in muscle performance, although the exact mechanism of estrogen-dependent sarcopenia remains to be clarified. Exercises have been shown to improve postmenopausal muscle performance and hormone replacement therapy may also potentiate these beneficial effects. Improvement or maintenance of muscle strength alone, however, may not be considered as a primary indication for long-term hormone replacement therapy in view of current knowledge of its risks and benefits. Work history and educational background may be associated with postmenopausal muscle performance, which itself has unique associations with skeletal and cardiovascular diseases.

Dietary protein intake is associated with better physical function and muscle strength among elderly women

Dietary protein intake might be beneficial to physical function (PF) in the elderly. We examined the cross-sectional and prospective associations of protein intake of g/kg body weight (BW), fat mass (FM) and lean mass (LM) with PF in 554 women aged 65·3-71·6 years belonging to the Osteoporosis Risk Factor and Prevention Fracture Prevention Study. Participants filled a questionnaire on lifestyle factors and 3-d food record in 2002. Body composition was measured by dual-energy X-ray absorptiometry, and PF measures were performed at baseline and at 3-year follow-up. Sarcopaenia was defined using European Working Group on Sarcopenia in Older People criteria. At the baseline, women with higher protein intake (≥ 1·2 g/kg BW) had better performance in hand-grip strength/body mass (GS/BM) (P=0·001), knee extension/BM (P=0·003), one-leg stance (P=0·047), chair rise (P=0·043), squat (P=0·019), squat to the ground (P=0·001), faster walking speed for 10 m (P=0·005) and higher short physical performance battery score (P=0·004) compared with those with moderate and lower intakes (0·81-1·19 and ≤ 0·8 g/kg BW, respectively). In follow-up results, higher protein intake was associated with less decline in GS/BM, one-leg stance and tandem walk for 6 m over 3 years. Overall, results were no longer significant after controlling for FM. Associations were detected between protein intake and PF in non-sarcopaenic women but not in sarcopaenic women, except for change of GS (P=0·037). Further, FM but not LM was negatively associated with PF measures (P<0·050). This study suggests that higher protein intake and lower FM might be positively associated with PF in elderly women.

Physical tests for patient selection for bone mineral density measurements in postmenopausal women

INTRODUCTION There is a need for cost-effective clinical methods to select women for bone densitometry. The aim of the present study was to determine whether relatively simple and clinically applicable physical tests could be useful in prediction of bone density in postmenopausal women. METHODS A total of 606 women (age range 66-71 years) taking part in the population based OSTPRE Fracture Prevention Study were investigated. Spinal and femoral bone mineral density (BMD) was measured by Dual X-ray Absorptiometry (DXA). Physical tests included the standing-on-one-foot (SOOF), grip strength (GS), leg extension strength, ability to squat down, standing 10 s eyes closed, chair rising, regular walk for 10 m and tandem walk for 6 m. All linear regression models were adjusted for age, body mass index, years on hormone therapy, years since menopause, current smoking and use of oral glucocorticoids. RESULTS The SOOF was associated with lumbar spine BMD (r2=0.16, p=0.004) and the femoral regions (r2 values from 0.17 to 0.23 and p-values all<0.001). The GS was associated with lumbar spine BMD (r2=0.16, p=0.011) and the femoral regions (r2 values from 0.16 to 0.21 and p-values from <0.001 to 0.004). The ability to squat down on the floor was associated with the femoral regions (r2 values from 0.15 to 0.21 and p-values from 0.028 to 0.040). In addition, functional capacity was decreased in women with femoral neck osteoporosis (WHO classification) compared to women with normal or osteopenic BMD: SOOF -39% (p=0.001), GS -18% (p<0.001), leg extension strength -19% (p=0.007) and ability to squat down on the floor -40% (p=0.004). For osteoporosis prediction (ROC analysis) a threshold of a 22 kg in GS would yield a true-positive rate (sensitivity) of about 58% and a true-negative rate (specificity) of 86% (AUC 0.76). CONCLUSIONS We suggest that grip strength could be used in medical decision making to identify those women who would benefit from BMD measurements albeit alone it may not provide accurate enough tool for osteoporosis screening.

Association of Grip Strength Change with Menopausal Bone Loss and Related Fractures: A Population-Based Follow-Up Study

The aim of the present study was to investigate the association between grip strength change and bone health according to menopausal status. A random sample of 971 pre- to postmenopausal women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort was measured with dual X-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN) and grip strength with pneumatic squeeze dynamometer at baseline (1989–1991), 5 years (1994–1997), and 10 years (1999–2001). Fractures were recorded based on self-reports and validated from medical records. Women were divided into two groups according to change in grip strength quartile from baseline to 5-year follow-up: not improved (n = 735) and improved (n = 236). In the total population, the greatest bone loss was observed in perimenopausal (beginning of menopause during follow-up, n = 311) women [P < 0.001 vs. premenopausal women (n = 139)], and it declined in postmenopausal (n = 521) women [P < 0.001 by analysis of covariance (ANCOVA)]. The perimenopausal bone loss rate was significantly lower in women in the improved group in comparison to the not improved group (P < 0.01) in contrast to the pre- and postmenopausal groups (P > 0.05). Accordingly, there was a greater decline in perimenopausal LS and FN T-scores in the improved group vs. the not improved group over the first 5-year follow-up interval (P < 0.05 by ANCOVA) and remained unchanged over the 10-year follow-up. In perimenopausal women, there was a trend toward higher fracture-free survival rate in the improved group (82%) vs. the not improved group (88%) after 10 years. Adjustments did not change the results. In conclusion, maintenance of grip strength is associated with menopausal bone loss and future fractures.

Dual-frequency ultrasound technique minimizes errors induced by soft tissue in ultrasound bone densitometry

Background: Most bone ultrasound devices are designed for through-transmission measurements of the calcaneus. In principle, ultrasound backscattering measurements are possible at more typical fracture sites of the central skeleton. Unfortunately, soft tissue overlying the bones diminishes reliability of these measurements. Purpose: To apply the single-transducer dual-frequency ultrasound (DFUS) technique to eliminate the errors induced by soft tissue on the measurements of integrated reflection coefficient (IRC) in human distal femur in vivo. Material and Methods: Ultrasound and dual-energy X-ray absorptiometry (DXA) examinations were conducted on a bodybuilder during a 21-week training and dieting period. Results: Significant changes in quantity and composition of soft tissue took place during the diet. However, DXA measurements showed no significant effects on bone density measurements. The single transducer DFUS technique enabled the determination of local soft-tissue composition, as verified by comparison with the DXA (r=0.91, n=8, p<0.01). Further, the technique eliminated the soft-tissue-induced error from IRC measured for the bone. The uncorrected IRC associated significantly with the change in local soft-tissue composition (r=−0.83, n=8, p<0.05), whereas the corrected IRC values showed no significant dependence (r=−0.30, n=8, p=0.46) on local soft-tissue composition. Conclusion: The DFUS technique may significantly enhance the accuracy of clinical ultrasound measurements of bone.