Joonas Sirola

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.

Relation of statin use and bone loss: a prospective population-based cohort study in early postmenopausal women.

Abstract: Recent experimental and epidemiologic studies have suggested that the lipid-lowering drugs, statins, may have bone-protective effects. We studied the effects of statin use on the change in bone mineral density (BMD) in a prospective 4.5-year cohort study based on subjects from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study, Finland. Six hundred and twenty women aged 53–64 years were divided into four groups: 55 women reported continuous and 63 women occasional statin use during the follow-up; 142 non-users of statins reported hypercholesterolemia whereas 360 non-users did not. Spinal and femoral BMDs were measured by dual-energy X-ray densitometry in 1995–1996 and 1999–2000 and the BMD changes of the four groups were compared. Characteristics of the study population were obtained with postal inquiries. The mean annual spinal and femoral BMD changes of the study groups were 0.29% and −0.50% for the continuous statin users, 0.19% and −0.57% for the occasional statin users, 0.52% and −0.29% for the hypercholesterolemic non-users of statins, and 0.39% and −0.33% for the non-users of statins without hypercholesterolemia, (p= 0.398 and p = 0.404) respectively. The corresponding BMD changes adjusted for age, years since menopause, body mass index, BMD at baseline, calcium intake, estrogen and cortisone therapy, duration of follow-up and statin use before the baseline were −0.20% and −0.47%, 0.19% and −0.54%, 0.54% and −0.32%, 0.47% and −0.33% (p= 0.134 and p= 0.628), respectively. Our results suggest that statins do not protect from early postmenopausal bone loss. Randomized trials are needed to confirm these results.

Factors affecting bone loss around menopause in women without HRT: a prospective study

OBJECTIVES The present study evaluated the effects of menopause and other putative bone loss modifying factors on bone mineral density (BMD) change. METHODS The study population, 396 healthy women aged 48-59 years with no history of hormone replacement therapy (HRT) use or any bone affecting disease or medications, was selected from a random sample (n=2025) of the OSTPRE-study cohort (n=13100) in Kuopio, Finland. BMD at lumbar spine (LS) and three areas of proximal femur (femoral neck (FN), Wards triangle (W), trochanter (T)) was measured with dual X-ray absorptiometry at baseline in 1989-1991 and at 5 years in 1994-1997. RESULTS 116 women who reported the beginning of menopause during the follow-up (perimenopausal) had the greatest mean annual bone loss (-1.22%/year (LS), -0.87% year (FN), -1.14%/year (W), -0.36%/year (T)). In women under 5 years postmenopausal at baseline (early postmenopausal, n=172) bone loss rate was significantly lower than in perimenopausal women. In women over 5 years postmenopausal at baseline (late postmenopausal, n=108) bone loss rate was significantly further decreased only at lumbar spine. In peri- and postmenopausal women the annual BMD change was best described as a trinomial function of the duration of menopause at all sites (P<0.03). Of the life-style factors studied protective effects were found in weight increase in both spinal and femoral bone (P=0.010/P<0.001), high baseline weight in spine (P<0.001) and high grip strength in femoral neck (P=0.002). CONCLUSION The beginning of menopause is accompanied by significant bone loss, which decreases in later menopause. Few other physiological and life-style factors were found to significantly contribute to this phenomenon.

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.

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.

Risk factors associated with peri- and postmenopausal bone loss: does HRT prevent weight loss-related bone loss?

Abstract In the present study we evaluated the risk factors associated with peri- and postmenopausal bone loss and the effect of hormone replacement therapy (HRT) on weight-loss-related bone loss. The study population, 940 peri- and postmenopausal women, was selected from a random sample (n = 2025) of the OSTPRE study cohort (n = 13 100) in Kuopio, Finland. Bone mineral density (BMD; g/cm2) at the lumbar spine and femoral neck, and body weight, were measured at baseline in 1989–91 and at 5-year follow-up in 1994–97 by trained personnel. Five hundred and forty-seven women had never used HRT and 393 women used part-time or continuous HRT during follow-up of 3.8–7.9 years (mean 5.8 years). Similarly, of the 172 weight losers, 97 had never used HRT while 75 used it during follow-up. According to multiple regression analysis on the total study population (n = 940), HRT use, years since menopause and weight increase significantly predicted lower annual bone loss at both the lumbar spine and femoral neck (p < 0.005). Low baseline weight and higher age predicted higher bone loss only at the lumbar spine (p < 0.001) and high grip strength predicted lower bone loss only at the femoral neck (p = 0.021). In a sub-analysis on weight losers, weight loss predicted greater bone loss in HRT non-users (p < 0.05), whereas this was not observed in HRT users. These results remained similar after adjustment for age, weight, height, calcium intake, duration of menopause, baseline BMD and bone-affecting diseases/medication. In conclusion, the transition to menopause, HRT and weight change are the most important determinants of bone loss at both the lumbar spine and femoral neck. Furthermore, HRT seems to be effective in prevention of weight loss related bone loss.

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.

Similarities in Acquired Factors Related to Postmenopausal Osteoporosis and Sarcopenia

Postmenopausal population is at increased risk of musculoskeletal impairments. Sarcopenia and osteoporosis are associated with significant morbidity and social and health-care costs. These two conditions are uniquely linked with similarities in pathophysiology and diagnostic methods. Uniform diagnostic criteria for sarcopenia are still evolving. Postmenopausal sarcopenia and osteoporosis share many environmental risk- and preventive factors. Moreover, geriatric frailty syndrome may result from interaction of osteoporosis and sarcopenia and may lead to increased mortality. The present paper reviews the factors in evolution of postmenopausal sarcopenia and osteoporosis.