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.

[Physiotherapy and exercise in osteoporosis and its complications]. / Physiotherapie und Bewegung bei Osteoporose und Folgeerkrankungen.

Osteoporosis is defined by decreased bone strength and increased susceptibility to fracture. Fractures and their consequences are the clinical manifestation of osteoporosis. Acute and chronic pain, functional limitations including permanent impairment and the need for long-term care may be caused by osteoporotic fractures. The aim of osteoporosis treatment is to prevent fractures by bone strengthening. The aims of rehabilitation in patients with osteoporosis are to reduce pain, maximize the level of musculoskeletal function, particularly following fractures, decrease risk of falls and optimize quality of life and independence. Certain sports and exercises greatly promote skeletal development in children and adolescents and augment bone strength in adults. Physiotherapy and therapeutic exercise may relieve pain, increase musculoskeletal function and form an important part of fall management.

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.

Long-term home exercise program: effect in women at high risk of fracture.

OBJECTIVE: To determine whether a better outcome in terms of physical frailty could be achieved with a regular home exercise program in women at high risk of fracture. DESIGN: Prospective long-term observational study. SETTING: Outpatient clinic of physical medicine and rehabilitation. PARTICIPANTS: Women with a history of postmenopausal fractures and an age-adjusted low bone mass, as determined 7 to 12 years earlier. INTERVENTION: Home exercise program. OUTCOME MEASURES: Thirty-three women were followed. The exercise group and control group were compared with regard to fracture rates, episodes of falling, neuromuscular performance (one-leg stance, chair rise, body sway, tandem walk, tapping test), and bone mineral density (BMD). RESULTS: Twenty-five women with a mean age of 73.8+/-5.7 yrs appeared for the investigation. An exercise program had been prescribed in 19 women, and six served as controls. Seven women of the exercise group (36.8%) regularly performed the exercises. No differences between participants of the groups in terms of fracture rates, falling episodes, neuromuscular performance, and BMD were observed. CONCLUSION: It appears that a home exercise program does not affect the outcome of postmenopausal women at high risk of fracture.

[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.

Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells.

Pathological degeneration of neurons in Huntington's disease and associated neurodegenerative disorders is directly correlated with the expansion of CAG repeats encoding polyglutamines of extended length. The physical properties of extended polyglutamines and the intracellular consequences of expression of polyglutamine expansion have been the object of intensive investigation. We have extended the range of lengths of polyglutamine produced by recombinant DNA methodology by constructing a library of CAG/CAA repeats coding for a range of 25-300 glutamine residues. We have investigated the subcellular localization, interaction with other polyglutamine-containing polypeptides, and the physical properties of aggregated forms of polyglutamine in the cell. Extended polyQ aggregated in the cytoplasm and was only transported to the nucleus when a strong nuclear localization signal was present. Polyglutamine below pathological lengths could be captured in aggregates and transported to ectopic cell locations. The CREB-binding protein (CBP), containing a homopolymeric stretch of 19 glutamines, was likewise found to coaggregate in a polyglutamine-dependent manner, suggesting that pathology in polyglutamine disease may result from cellular depletion of normal proteins containing polyglutamine. We have observed a striking detergent resistance in aggregates produced from polyglutamine of pathological length. This observation has led to the development of a fluorescence-based assay exploiting the detergent resistance of polyglutamine aggregates that should facilitate high-throughput screening for agents that suppress polyglutamine aggregation in cells.

Evidence for a recruitment and sequestration mechanism in Huntington's disease.

Polyglutamine (polyQ) extension in the coding sequence of mutant huntingtin causes neuronal degeneration associated with the formation of insoluble polyQ aggregates in Huntington's disease. We constructed an array of CAG/CAA triplet repeats, coding for a range of 25-300 glutamine residues, which was used to generate expression constructs with minimal flanking sequence. Normal-length (25 glutamine residues) polyQ did not aggregate when transfected alone. Remarkably, when co-transfected with extended (100-300 glutamine residues) polyQ tracts, normal-length polyQ-containing peptides were trapped in insoluble detergent-resistant aggregates. Aggregates formed in the cytoplasm but were visible in the nucleus only when a strong nuclear localization signal was present. Intermolecular interactions between polyQ tracts mediated the localization of heterogeneous aggregates into the nucleolus by nucleolin protein. Our results suggest that extended polyQ can interact with cellular polyQ-containing proteins, transport them to ectopic cellular locations, and form heterogeneous polyQ aggregates. We provide evidence for a recruitment mechanism for pathogenesis in the polyQ neurodegenerative disorders. In susceptible cells, extended polyQ tracts in huntingtin might interact with and sequester or deplete certain endogenous polyQ-containing cellular proteins.

Ultrasound therapy for calcific tendinitis of the shoulder.

BACKGROUND AND METHODS: Although ultrasound therapy is used to treat calcific tendinitis of the shoulder, its efficacy has not been rigorously evaluated. We conducted a randomized, double-blind comparison of ultrasonography and sham insonation in patients with symptomatic calcific tendinitis verified by radiography. Patients were assigned to receive 24 15-minute sessions of either pulsed ultrasound (frequency, 0.89 MHz; intensity, 2.5 W per square centimeter; pulsed mode, 1:4) or an indistinguishable sham treatment to the area over the calcification. The first 15 treatments were given daily (five times per week), and the remainder were given three times a week for three weeks. Randomization was conducted according to shoulders rather than patients, so a patient with bilateral tendinitis might receive either or both therapies. RESULTS: We enrolled 63 consecutive patients (70 shoulders). Fifty-four patients (61 shoulders) completed the study. There were 32 shoulders in the ultrasound-treatment group and 29 in the sham-treatment group. After six weeks of treatment, calcium deposits had resolved in six shoulders (19 percent) in the ultrasound-treatment group and decreased by at least 50 percent in nine shoulders (28 percent), as compared with respective values of zero and three (10 percent) in the sham-treatment group (P=0.003). At the nine-month follow-up visit, calcium deposits had resolved in 13 shoulders (42 percent) in the ultrasound-treatment group and improved in 7 shoulders (23 percent), as compared with respective values of 2 (8 percent) and 3 (12 percent) in the sham-treatment group (P=0.002). At the end of treatment, patients who had received ultrasound treatment had greater decreases in pain and greater improvements in the quality of life than those who had received sham treatment; at nine months, the differences between the groups were no longer significant. CONCLUSIONS: In patients with symptomatic calcific tendinitis of the shoulder, ultrasound treatment helps resolve calcifications and is associated with short-term clinical improvement.

Functional impact of unvarying exercise program in women after menopause.

Low bone mass, functional impairment, low muscle strength, and postural instability are predictors of the risk of fracture in an elderly person. The purpose of this study was to investigate the functional impact of an unvarying long-term exercise program to be carried out at home. The exercises had been shown to delay bone loss in an elderly population. At the Department of Physical Medicine and Rehabilitation, University of Vienna, postmenopausal women who had been stratified into exercise or control groups 5 to 10 yr ago were called in for a follow-up examination. Frequency of training, habits, and pain causing disability in activities of daily living were recorded. Walking velocity, muscle strength, and postural stability were measured. Functional assessment, blood analysis, and x-rays of the spine were performed additionally. One hundred twenty-four women aged 68.3 +/- 6.8 yr (mean +/- SD) underwent a follow-up investigation at the outpatient clinic. After 7.7 +/- 1.1 yr the compliance of the training group was still 36%. Self-chosen gait velocity was slightly higher in the regular exercisers than in the controls. No intergroup differences were found for pain induced disability, muscle strength, body sway, and fracture rate. The pain disability index was significantly associated with corrected self-chosen gait velocity. The results suggest that an unvarying home-based exercise program may support general agility but does not yield enough force to improve muscle strength and postural stability in healthy, nondisabled, postmenopausal women who start exercising at the age of 60 yr. Further studies are needed to define more appropriate exercise programs for a comprehensive improvement of functional outcome in a population at high risk for osteoporosis.

[Value of impedance rheography as a screening method in comparison with Doppler index in peripheral arterial occlusive disease]. / Wertigkeit der Impedanzrheographie als Screeningmethode im Vergleich zum Doppler-Index bei peripherer arterieller Verschlusskrankheit.

BACKGROUND: Determination of the ankle-arm-index (AAI) by Doppler ultrasound is the method of choice as a screening test for peripheral arterial occlusive disease (PAOD). The easily performed Impedance Rheography (IR) may serve as an alternative screening method. This study investigates the correlations between parameters obtained by IR curve to the AAI. METHODS: 56 patients (62.8 +/- 13 years, m = 37, f = 19) were included in the study. IR was performed on both shanks using ring electrodes below the knee and above the ankle (bipolar leads, frequency 90 kHz, test voltage 2.5 Vpp). The AAI was obtained by a 8 Mz ultrasound probe. RESULTS: AAI < or = 0.85 showed significant correlations (p < 0.0001) to parameters of the IR curve: Crest Time (GZ, r = 0.67), Rise of the Pulse Wave (PA, r = 0.82), Relative Pulse Volume (RP, r = 0.82) and the Rheographic Quotient (RQ, r = 0.86). AAI > 0.85 showed no or only weak correlations to RI parameters. Underlying the following limits for rheographic parameters (GZ = 159 ms, PA = 3.3, RP = 0.43 vp/s and RQ = 0.4 vp), sensitivity and specify was determined: GZ: 68% and 100%, PA: 84% and 88%, RP: 68% and 92%, RQ: 77% and 88%. CONCLUSIONS: Impedance rheography correlates significantly with the AAI. Therefore this method seems to be well suited as a screening test for PAOD.

Fluorescence endoscopic imaging of human colonic adenomas.

BACKGROUND & AIMS: Endoscopic screening for sporadic colorectal cancer relies in part on the detection of adenomatous polyps. Nonpolypoid adenomas or flat dysplasia may go unrecognized by conventional endoscopy. This study attempted to develop and test a novel endoscopic method for detecting polypoid and nonpolypoid colonic adenomas. METHODS: Colectomy specimens from 3 patients with familial adenomatous polyposis containing polypoid and nonpolypoid adenomas were illuminated with excitation light at 351 and 364 nm. Endoscopic images of the net tissue fluorescence emitted were collected over the spectral bandwidth from 400 to 700 nm. Each raw image was corrected for differences in distance and instrument light collection efficiency by normalizing to a spatially averaged image. Intensity thresholding was then used to identity regions of diseased mucosa. RESULTS: The average fluorescence intensity from normal mucosa was found to be greater than that from adenomas by a factor of 2.2 +/- 0.6. The sensitivity and specificity for detecting a region of dysplasia varied with the threshold value selected. At a threshold of 75% of the average normal intensity, a sensitivity of 90% and a specificity of 92% were achieved. CONCLUSIONS: Fluorescence images of colonic mucosa can be collected endoscopically, and dysplasia can be detected and localized with high sensitivity and specificity. These results show the potential of this technique to direct endoscopic biopsy.

Exercise therapy for osteoporosis: results of a randomised controlled trial.

OBJECTIVE: To define the effects of therapeutic exercise on bone density and back complaints. METHODS: A randomised controlled trial with parallel groups was conducted in an outpatient clinic, Medical School, University of Vienna. Ninety two sedentary post-menopausal women with back problems were randomly allocated to either exercise (groups 1 and 2) or control (group 3, no exercise, n = 31); the exercise group was retrospectively subdivided into compliant (group 1, n = 27) and not fully compliant patients (group 2, n = 34). Regular, initially supervised therapeutic exercise aimed at restoring biomechanical function was performed for four years. Bone density in the forearm was measured by single photon absorptiometry at entry and after four years; subjective back complaints were documented. RESULTS: A significant decrease in bone density was observed in groups 2 and 3; no change was noted in group 1; back complaints decreased in group 1 only. CONCLUSIONS: Sedentary postmenopausal women may benefit from regular long term therapeutic exercise in terms of subjective back complaints and slowed loss of bone mass.

Systematic strength training as a model of therapeutic intervention. A controlled trial in postmenopausal women with osteopenia.

Physical exercise is often recommended as a therapeutic tool to combat pre- and postmenopausal loss of bone density. However, the relationship between training dosage (intensity, duration, frequency) and the effect on bone density still is undergoing discussion. Furthermore, the exercise quantification programs are often described so inadequately that they are neither quantitatively nor qualitatively reproducible. The aim of this investigation was to determine whether a clearly defined training of muscle strength, under defined safety aspects, performed only twice weekly, can counteract bone density loss in women with postmenopausal osteopenia. Data from 16 women in the training group (age, 63.6 +/- 6.2 yr) and 15 women in the control group (age, 67.4 +/-9.7 yr), of comparable height and weight, were evaluated. Strength training was performed for 6 mo as continually adapted strength training, providing an intensity of about 70% of each test person's one repetition maximum. Bone mineral density of lumbar vertebrae 2 to 4 and the femoral neck was measured by dual-energy x-ray absorptiometry. Maximum performance in watts and parameters of hemodynamics were controlled with a bicycle ergometer test to maximal effort. In addition, metabolic data were assessed. In the lumbar spine and femoral neck, the training group showed no significant changes, whereas the control group demonstrated a significant loss of bone mineral density, especially in the femoral neck (P<0.05). The strength increase was highly significant in all exercised muscle groups, rising to about 70% above the pretraining status (P<0.001). Heart rate and blood pressure data indicated a slight economization, metabolism was not significantly influenced. Based on these findings, we conclude that continually adapted strength training is an effective, safe, reproducible, and adaptable method of therapeutic strength training, following only two exercise sessions per week.

Therapeutic exercise in the prevention of bone loss. A controlled trial with women after menopause.

To evaluate the efficacy of therapeutic exercises in the prevention of bone loss, 146 untrained healthy postmenopausal women were prospectively controlled for (mean +/- SD) 3.0 +/- 1.3 yr. Eighty-two subjects aged (mean +/- SD) 61.5 +/- 6.1 yr participated in an exercise program (group 1) and sixty-four aged (mean +/- SD) 59.1 +/- 7.4 yr served as controls (group 2). Periodically during the study period, we measured women's bone density at two forearm sites and recorded their physical activities. Because bone loss differed insignificantly between the groups, group 1 was retrospectively subdivided into group 1a (regular exercise) and group 1b (nonregular exercise). The results showed that only 39 women (48 percent) of group 1 (group 1a) performed the exercise program regularly for the prescribed time. Regression slopes of forearm bone density (distal and proximal scans) v time were significantly less negative (P < 0.05) in group 1a (distal, -0.3 percent and proximal, -0.7 percent per year) than in group 1b (distal, -1.8 percent and proximal -1.6 percent per year) or group 2 (distal, -1.7 percent and proximal, -1.9 percent per year). We conclude that in untrained elderly women, poor compliance with regular physical activities is a main factor, explaining the lack of response to exercise treatment in prevention of osteoporosis.