Effects of different exercise intensity on bone mineral density in adults: a comparative systematic review and meta-analysis.

PURPOSE: The primary objective of the present systematic review and meta-analysis was to determine the effect of differing exercise intensity on (areal) bone mineral density (BMD) at lumbar spine and hip in adults by a comparative meta-analysis. METHODS: A systematic review of the literature according to the PRISMA statement included: (a) exercise trials, (b) with ≥two study arms that compared different exercise intensities, (c) intervention ≥6 months, (d) BMD assessments at lumbar spine (LS) or hip. Five electronic databases were scanned without language restrictions up to July 2021. The present analysis of exercise intensity was conducted as a mixed-effect meta-analysis and applied "type of exercise" and "study duration" as moderator in subgroup analyses. Outcome measures were standardized mean differences (SMD) for BMD changes at the LS, and hip. RESULTS: Eleven exercise studies with 26 study arms were included. Although the effect of high-intensity exercise was more pronounced on LS-BMD (SMD: 0.19, 95%-CI: 0.61 to -0.23) and hip-ROI (0.17, 0.38 to -0.04), we did not observe significant differences between the groups (LS-BMD: p=0.373 and hip-BMD: p=0.109). We observed a substantial level of heterogeneity between the trials for LS- but not for hip-BMD. Applying "type of exercise" and "study duration" as moderators did not significantly modify the differences between low and high exercise intensity on BMD at LS or hip. CONCLUSION: There is insufficient evidence for a superior effect of high-intensity exercise on areal BMD at lumbar spine and hip in people aged 50 years and older. Varying exercise intensity with periods of lower exercise intensity intermitted by higher intensity might be a promising option to address the issue of exercise intensities in intervention studies.

Diagnostic Performance of a Panel of miRNAs (OsteomiR) for Osteoporosis in a Cohort of Postmenopausal Women.

A specific signature of 19 circulating miRNAs (osteomiRs) has been reported to be associated with fragility fractures due to postmenopausal osteoporosis. However, it is unknown whether osteoporotic fractures or low BMD phenotypes are independently contributing to changes in osteomiR serum levels. The first aim was to characterize the abundance, sensitivity to hemolysis, and correlation of osteomiR serum levels, the second objective to evaluate the diagnostic accuracy of osteomiRs for osteoporosis according to the WHO criteria and on basis of major osteoporotic fracture history. Fifty postmenopausal women with osteoporosis (with or without fragility fracture) and 50 non-osteoporotic women were included in this cross-sectional study. The diagnostic performance of osteomiRs for osteoporosis based on the WHO definition or fracture history was evaluated using multiple logistic regression and receiver-operator curve (AUC) analysis. The osteomiR® signature is composed of four clusters of miRNAs providing good performance for the diagnosis of osteoporosis in postmenopausal women defined by WHO criteria (AUC = 0.830) and based on history of major osteoporotic fractures (AUC = 0.834). The classification performance for the WHO criteria and for fracture risk is driven by miR-375 and miR-203a, respectively. OsteomiRs, a signature of 19 emerging miRNA bone biomarkers, are measurable in human serum samples. They constitute a panel of independent bone and muscle biomarkers, which in combination could serve as diagnostic biomarkers for osteoporosis in postmenopausal women.

Current controversies in clinical management of postmenopausal osteoporosis.

Osteoporosis is a frequent disease in postmenopausal women. Despite the fact that fragility fractures cause many problems - a bio-psycho-social burden for the individual and an economic burden for the society - osteoporosis is still underdiagnosed and undertreated. Controversies exist concerning assessment with different tools for initiating a disease-specific treatment, patient monitoring with bone turnover markers, and treatment duration due to potential side effects in long-term treatment. This manuscript outlines and discusses these controversies and the presented cases, representatives for frequent clinical problems, may give guidance for the clinician in deciding how and how long to treat his/her patient. Re-evaluations of the patients on a regular basis are essential to warrant the necessity of treatment continuation and may improve patients' compliance.

How long should women with postmenopausal osteoporosis be treated with a bisphosphonate?

Bisphosphonates are very frequently prescribed to women suffering from postmenopausal osteoporosis with or without fragility fractures. The present review was aimed to update the available information on the most efficient treatment duration. Studies on bisphosphonate treatment duration were identified by Medline up to January 2013. Bisphosphonates are very effective in the short as well as in the medium-term. However, the optimal duration of use has not been determined yet. Therefore, this review summarizes the long-term effects of bisphosphonates on surrogate parameters of fracture prevention, bone mineral density measurements, and bone turnover markers. An initial treatment period of 3-5 years is recommended. Then, the patient has to be re-evaluated for fracture risk, which depends on fracture status as well as on other health issues. Beyond that, life style factors such as regular physical activity as well as a sufficient intake of calcium and vitamin D or, if necessary supplementation of calcium and/or vitamin D play an essential part in fracture prevention.

Bone metabolism in patients with primary hyperparathyroidism before and after surgery.

Primary hyperparathyroidism (PHPT) is accompanied with a reduced bone mineral density (BMD) and an increased risk of fracture. Surgery is the only option for cure. It is hypothesized that in patients with PHPT bone metabolism normalizes after parathyroidectomy (PTX) and that BMD gradually increases. Fifty-two patients with PHPT who underwent surgery were prospectively followed for 1 year. Biochemical analyses were performed at baseline and 1, 4, 7 days; 6 weeks; and 3, 6, and 12 months, and BMD before and one year after surgery. Parathyroid hormone (PTH), calcium, and the bone resorption marker dropped immediately, but transiently after PTX, bone formation decreased more slowly. Osteoprotegerin (OPG) as well as cathepsin K did not show significant changes. BMD of the lumbar spine, but not of the femoral neck, increased significantly within one year after surgery. Moderate correlations existed between the changes of total calcium, ionized calcium, as well as bone-specific alkaline phosphatase and changes of the lumbar BMD. Patients who needed postoperative supplementation with calcium and vitamin D had significantly higher PTH levels. Some gender-specific differences in patients with PHPT were observed. In patients with PHPT, males appear to be more severely affected than females. Within the first year after PTX, bone metabolism normalized, and BMD of the lumbar spine increased. Patients who needed a supplementation with calcium and vitamin D after PTX preoperatively had higher serum levels of PTH.

Serum levels of receptor activator of nuclear factor kappaB ligand (RANKL) in healthy women and men.

BACKGROUND: Osteoporosis is one of the most common conditions associated with aging. It is based on an excess of bone resorption over bone formation, leading to an imbalance of bone turnover. The receptor activator of nuclear factor kappaB ligand (RANKL) is an important regulator of bone metabolism. OBJECTIVE: The aim of this investigation was to evaluate potential age- and gender-related changes in free RANKL and total RANKL (free RANKL+RANKL/osteoprotegerin complexes). METHODS: Two hundred and forty volunteers with a median age of 48 years were included in the study. Serum levels of free RANKL and total RANKL were evaluated. RESULTS: On average, men have a 1.77-fold higher free RANKL level and a 2.12-fold higher free/total RANKL ratio than women of the same age. On average, the RANKL levels decrease by approximately 13% every five years. CONCLUSION: This study showed that serum levels of free RANKL and total RANKL decrease with age, and also revealed some gender-related differences.

Serum levels of cathepsin K decrease with age in both women and men.

Bone turnover increases with age. In a previous study, we reported on bone metabolism in young and elderly women and men. The aim of the present investigation was to evaluate potential age- and gender-related changes in cathepsin K, a cysteine protease that plays an important role in the degradation of the organic matrix of bone. Twenty-five healthy premenopausal women, 24 young healthy men, 26 elderly women, and 25 elderly men participated in the study. Elderly women and men had significantly lower cathepsin K levels than younger ones. In both men and women, serum levels of cathepsin K were negatively correlated with age. In men there was a statistically significant negative correlation between serum levels of cathepsin K and osteoprotegerin, which inhibits osteoclast differentiation and activation. No association was found between serum levels of cathepsin K and bone-specific alkaline phosphatase, osteocalcin, or 25-hydroxy vitamin D. Thus, the age-related increase in OPG, which markedly inhibits the expression of cathepsin K, may also reduce serum levels of cathepsin K. Despite the age-related increase in bone resorption, this study shows lower cathepsin K values in elderly women and men than in younger subjects. It might be speculated that a different enzyme could compensate for the decline in cathepsin K during old age.

Bone metabolism in patients more than five years after bone marrow transplantation.

We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG)--antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P=0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.

Reliability of pelvic floor muscle strength measurement in elderly incontinent women.

Pelvic floor muscles (PFM) play an important role in maintaining urinary continence with increasing age. Therefore, their contractile properties need to be evaluated. The aim of the study was to examine the reliability and correlation of simple techniques to measure PFM strength in elderly women with urinary incontinence. An interview was used to evaluate the ability to stop the urinary stream during micturition and to calculate the incontinence index. A pad test was applied to objectively evaluate the severity of the disease. Functional testing included a digital examination to measure the force and duration of one contraction, a perineometer measurement (Peritron) to assess maximal contraction force and contraction force of 5 s, and a cone-retention test (Femcon) while walking for 1 min and during Valsalva's manoeuvre. This procedure was performed on three separate occasions within one week. The 37 participating women with a mean age of 62+/-8 (mean+/-SD) years had a severity index of 4.4+/-2.6 and a urine loss of 9.5+/-13.6 mg during the pad test. Sixteen women were able to completely stop the urinary stream during micturition. The digital examination showed no intratester variability. The perineometer measurement showed that the absolute difference in maximal contraction force and mean contraction force within 5 s was less than 5.3 mm Hg and 4.5 mm Hg, respectively, with a probability of 0.95. While walking and during Valsalva's manoeuvre, 19 and 20 women, respectively, held the same cone in place on all three occasions. The maximal contraction force and mean force during the 5-s contraction correlated well with the ability to stop the urinary stream and the digital examination but only weakly with the cone-retention tests. The reliability of PFM strength measurement is highest in the digital examination, followed by perineometer measurements, and then by vaginal cone tests. As PFM function is easy to assess, it should be routinely done in the assessment of urinary incontinence in elderly women.

The effect of calisthenic home exercises on postmenopausal fractures--a long-term observational study.

OBJECTIVES: To evaluate the long-term effects of calisthenic home exercises on the incidence of fractures in postmenopausal women. DESIGN: Controlled long-term observational study. METHODS: Postmenopausal women between 45 and 75 years of age who had been randomly assigned to an exercise or control group in the course of a previous study conducted 5-10 years ago, were invited for follow-up. The number of fractures before and during the observation time were recorded by means of a questionnaire. Vertebral deformities due to fractures were diagnosed by X-rays at entry and at follow-up. Walking speed, muscle strength, static posturography, and maximum oxygen uptake were measured in addition. RESULTS: After an average follow-up time of 7.6+/-1.1 years, 73 women of the exercise group and 64 subjects of the control group were investigated. Thirty-three per cent (n=24) of the exercise group reported to have exercised continuously at least three times a week for 20 min. No intergroup differences between the compliant and non-compliant exercisers and the control group were seen in the number of fractures. However, the incidence of fracture was lowest in women with a baseline bone mass less than one standard deviation (SD) below the mean for young adults (high BMC) and highest in those with more than 2.5 SD below the mean for young adults (low BMC) (P<0.001, odds ratio 2.9 [95% CI, 1.59-5.39]). CONCLUSION: This long-term follow-up did not produce any evidence that prescription of a calisthenic home exercise program may prevent fractures in postmenopausal women aged between 61+/-6.4 and 68+/-6.5 years.

Immune phenotype and intracellular cytokine production of peripheral blood mononuclear cells from postmenopausal patients with osteoporotic fractures.

A number of factors with known effects on bone turnover are also immune regulatory factors. Disturbances of bone remodeling thus may be a consequence of altered local immune reactivity. We therefore determined surface markers and intracellular cytokine production of peripheral blood mononuclear cells by four-color flow cytometry in 19 postmenopausal patients with established osteoporosis and a control group of 11 postmenopausal women without fragility fractures. No significant differences in bone mineral density as assessed by dual energy X-ray absorptiometry were observed between the two groups. The following surface markers and cytokines were studied: CD3, CD4, CD8, CD16, CD19, CD29, CD45RA, CD56, CD57, HLA-DR, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-13, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte macrophage colony stimulating factor. In the fracture patients, the percentage of CD8+ cells co-expressing CD57 was increased (14+/-2 vs. 8+/-1%; p=0.03). Moreover, the proportion of CD8+ cells co-expressing TNF-alpha (47+/-5 vs. 33+/-4; p=0.05) and both TNF-alpha and IFN-gamma was significantly higher in the patients than the controls (41+/-6 vs. 22+/-3%; p=0.04). IL-1beta expression tended to be increased in monocytes from patients with established osteoporosis. Distinct subsets of CD8+ cells thus appear to contribute to the development of osteoporotic fractures.

Markers of bone turnover in postmenopausal women receiving hormone replacement therapy.

We investigated the effects of hormone replacement therapy (n = 27) on biochemical markers of bone turnover in a cross-sectional study of 127 postmenopausal women (according to WHO guidelines 18 patients had normal bone mineral density and 109 suffered from bone loss). Urinary excretion of free deoxypyridinoline and C- or N-telopeptide fragments of type I collagen served as bone resorption markers, serum osteocalcin as a bone formation marker. In women with no hormone replacement therapy, only C- and N-telopeptides correlated significantly with the lumbal T-score as an index for bone mineral density. Patients with bone loss receiving hormone replacement therapy exhibited significantly lower C-telopeptide, N-telopeptide and osteocalcin levels than those with no therapy (mean -45%, -43% and -26%, respectively), while deoxypyridinoline showed no significant differences. Among the markers investigated, C- and N-telopeptides seemed to be more reliable to detect therapeutic effects on bone metabolism. We present a preliminary model to evaluate bone turnover and resorption/formation rate.

Whole-body vibration exercise leads to alterations in muscle blood volume.

Occupationally used high-frequency vibration is supposed to have negative effects on blood flow and muscle strength. Conversely, low-frequency vibration used as a training tool appears to increase muscle strength, but nothing is known about its effects on peripheral circulation. The aim of this investigation was to quantify alterations in muscle blood volume after whole muscle vibration--after exercising on the training device Galileo 2000 (Novotec GmbH, Pforzheim, Germany). Twenty healthy adults performed a 9-min standing test. They stood with both feet on a platform, producing oscillating mechanical vibrations of 26 Hz. Alterations in muscle blood volume of the quadriceps and gastrocnemius muscles were assessed with power Doppler sonography and arterial blood flow of the popliteal artery with a Doppler ultrasound machine. Measurements were performed before and immediately after exercising. Power Doppler indices indicative of muscular blood circulation in the calf and thigh significantly increased after exercise. The mean blood flow velocity in the popliteal artery increased from 6.5 to 13.0 cm x s(-1) and its resistive index was significantly reduced. The results indicate that low-frequency vibration does not have the negative effects on peripheral circulation known from occupational high-frequency vibration.

A neuromuscular test battery for osteoporotic women: a pilot study.

OBJECTIVE: To examine the efficacy of a short neuromuscular test battery in elderly women suffering from osteoporosis in accordance with the World Health Organization criteria, with and without a history of fractures. Reduced bone mass and a high likelihood of falling increase the risk of osteoporotic fractures. There is a need for neuromuscular tests to identify individuals at risk for falls and fractures. DESIGN: The women were assessed twice. Forty-two women, with a mean age of 70.0 +/- 5.1 (SD) yr, completed the first assessment. The number of postmenopausal fractures and the women's history with regard to agility and falls were assessed. The women performed neuromuscular tests (one-leg stance, tandem walk, and body sway); bone mineral density of the spine and femoral neck were measured. For the follow-up assessment, 13.2 +/- 1.3 mo later, 39 women were studied. The same outcome measurements were obtained at both evaluations. RESULTS: During the observation period, five women fell once and one woman fell twice; there were only two vertebral fractures and no nonvertebral fracture. Neuromuscular performance did not change during this observation period. The median changes in bone mineral density between the two assessments were clinically not relevant. A comparison between patients suffering from established osteoporosis and osteoporotic patients without a history of postmenopausal fractures showed that both groups of patients did not differ with respect to age, neuromuscular performance, bone mineral density, and fear of falling. CONCLUSION: This neuromuscular test battery is a feasible and practical tool because it is brief and economical to perform. However, its efficacy as a predictor of fractures must be tested in additional studies with a long-term follow-up and a larger group of subjects.

[Translation of the Osteoporosis Quality of Life questionnaire (OQLQ) into German]. / Anwendung des in die deutsche Sprache übersetzten Osteoporosis Quality of Life Questionnaire (OQLQ).

Osteoporosis is a major health problem affecting the quality of life. The Osteoporosis Quality of Life Questionnaire (OQLQ) is a disease-specific measure intended for use in English-speaking countries. As there is a need for measures in non English-speaking countries as well, we translated the OQLQ according to a standardised protocol into the German language. Twenty-five women suffering from osteoporosis were tested in regard of quality of life. The questionnaire appears to be especially suitable for more disabled patients.

[Cold and cryotherapy. A review of the literature on general principles and practical applications]. / Kälte- und Kryotherapie. Eine Literaturübersicht über Grundlagen und praktische Anwendungen.

Cryotherapy increases the threshold of pain and induces physiological changes. It influences hemodynamics (reduction of skin- and muscle temperature through vasoconstriction), metabolism (reduction of ischemia due to hypoxia), and neural control (reduction of nerve conduction velocity and muscle tone). Cryotherapy is indicated mainly in locomotor system related pain. Such pain can be induced by degenerative changes, postoperatively, and during mobilisation of contracted joints. Cryotherapy may be used as short term therapy (less than 15 min) as well as long term therapy (more than 20 min). For maximal efficacy the intensity of application as well as the application medium must be considered. Due to biorhythm, cold application seems to be more effective in the afternoon.