Osteology: further debate.
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Bone Diseases, Metabolic↗
Biomedical subjects
R Marcus
Publications and source records attributed to R Marcus.
The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial.
We assessed the associations of eight bone turnover markers (BTMs) with baseline and 1-year percentage changes in lumbar spine and hip bone mineral density (BMD) of 293 postmenopausal women undergoing treatment with hormone replacement therapy (HRT) or placebo using squared correlation coefficients (R2). In 239 women assigned to treatment with estrogen alone or with with estrogen plus progestins (active treatment), mean percentage changes for all markers decreased significantly and remained below baseline values through 3 years of study, whereas mean percentage changes for 54 women assigned to the placebo group showed no significant change from baseline in any marker. At baseline, age and body mass index (BMI) together accounted for 16% and 25% of the variance in spine and hip BMD, respectively. The telopeptide resorption marker, cross-linked N-telopeptide of type I collagen (NTX), alone accounted for 12% and 8% of variance, respectively. Another telopeptide, carboxy-terminal telopeptide of type I collagen (Crosslaps), accounted for 8% and 7% of variance, respectively. A bone-specific alkaline phosphatase (BALP-2) accounted for 8% of variance at the spine and 5% at the hip. No other marker accounted for more than 5% of total variance at either site; adding either baseline NTX, Crosslaps, or BAP-2 to regressions containing age and BMI increased R2 values at the spine and hip to about 22% and 28%, respectively. In the placebo group, baseline spine BMD accounted for 4% of the variance in 1-year spine BMD percentage change, whereas baseline values for age and BMI accounted for 1% and 0% of the variance, respectively; none of the three accounted for more than 0% of hip BMD percentage change; Crosslaps and NTX contributed 5% and 4% to the variance in 1-year spine BMD percentage change, but other markers accounted for < 2% of variance at the spine. At the hip, another BALP (BALP-1) accounted for 4% of variance, but no other baseline marker except NTX accounted for more than 1% of variance. In the active treatment group, baseline values for age, BMI, and spine BMD together accounted for 13% of the percentage change in spine BMD and for 4% of the BMD change at the hip. No individual or pair of baseline markers significantly enhanced these R2 values, but addition of 1-year percentage changes in some individual markers did significantly increase it. The largest R2 value was obtained by adding the percentage change in BALP-2, which increased the R2 in spine BMD percentage change to 20% and that at the hip to 8%. Adding baseline and change variables for all eight markers to the regression increased R2 to 28% at the spine and 12% at the hip. Restricting the set of analyses to individuals who suppressed marker activity beyond the precision error for the measurement did not improve R2s for the regressions. When baseline marker values were stratified into quartiles, only NTX and osteocalcin showed significant relationships between quartile and change in spine BMD, and these did not reach significance at the hip. When the 1-year change in markers was stratified into quartiles, significant relationships with percentage change in spine BMD were observed only for BALP phosphatases. We conclude that BTMs are not a surrogate for BMD to identify women with low bone mass and that they offer little useful information for predicting BMD changes for individual untreated or HRT-treated postmenopausal women.
Alkaline Phosphatase↗
Lack of association of anabolic hormone status and muscle strength with regional and whole body bone mineral density in healthy men aged 60-79 years.
This study investigated the capacity of muscle strength and anabolic hormone status to predict regional and whole body bone mineral density (BMD) in older men. Fifty-two healthy men aged 60-79 years served as subjects. BMD of the lumbar spine, proximal femur, upper and lower limbs, and whole body was assessed by dual X-ray absorptiometry. Dynamic muscle strength for several upper and lower body muscle groups was determined by the one-repetition maximum and isometric grip strength by dynamometry. Anabolic hormone status was assessed by the ratio of testosterone (T) to sex hormone binding globulin (SHBG), given as the free androgen index (FAI), and the ratio of insulin-like growth factor I (IGF-I) to IGF binding protein-3 (IGFBP-3). Age was associated with declines in dynamic strength and the log FAI. In stepwise regression analysis, only body mass was an independent predictor of whole body and upper limb BMD (R2 = 0.13), and hip adductor strength predicted the Ward's triangle (R2 = 0.14). For lumbar spine BMD, triceps extensor strength was significantly correlated (r = 0.36, p < 0.01), while no strength or hormonal variable was associated with the femoral neck, trochanter, or lower limb. The lack of association between muscle strength and BMD was generally unaltered after controlling for hormone status and body mass. There was no difference in BMD when analyzed by tertiles of log FAI or IGF-I/IGFBP-3 or by tertiles of muscle strength. These results suggest that in healthy community-dwelling men in the seventh and eighth decade, muscle strength and hormonal status are not significant contributors to regional or whole body BMD.
Aged↗
Use of bone alkaline phosphatase to monitor alendronate therapy in individual postmenopausal osteoporotic women.
BACKGROUND: Biochemical bone markers are sensitive to the changes in bone turnover that result from treatment of postmenopausal osteoporotic women with antiresorptive therapies. Although information is available on the use of bone markers in monitoring therapy in groups of subjects, less is known regarding how these markers perform in individual patients. METHODS: Serum bone alkaline phosphatase (bone ALP) concentrations, measured with the Tandem(R) Ostase(R) assay, were used to monitor the biochemical response of bone in postmenopausal women with osteoporosis receiving either 10 mg/day alendronate therapy (n = 74) or calcium supplementation (n = 148) for 24 months. RESULTS: Bone ALP decreased significantly from baseline at 3 months (P </=0.0001), reaching a nadir between 3 and 6 months of alendronate therapy. The magnitude of the bone ALP decrease in the treated osteoporotic population was consistent with normalization to premenopausal concentrations. Of the 74 alendronate-treated subjects, 63 (85.1%) demonstrated a decrease from baseline in bone ALP by 6 months that exceeded the least significant change of 25%. The bone ALP decrease from baseline exceeded 25% in 72 (97%) by the end of the study. CONCLUSION: The bone ALP assay is a sensitive and reliable tool that may be used to monitor the reduction in bone turnover after alendronate therapy in individual postmenopausal osteoporotic women.
Aged↗
Regional and total body bone mineral density in elite collegiate male swimmers.
BACKGROUND: To examine the role of long-term swimming exercise on regional and total body bone mineral density (BMD) in men. METHODS EXPERIMENTAL DESIGN: Cross-sectional. SETTING: Musculoskeletal research laboratory at a medical center. PARTICIPANTS: We compared elite collegiate swimmers (n = 11) to age-, weight-, and height-matched non-athletic controls (n = 11). MEASURES: BMD (g/cm2) of the lumbar spine (L2-4), proximal femur (femoral neck, trochanter, Ward's triangle), total body and various subregions of the total body, as well as regional and total body fat and bone mineral-free lean mass (LM) was assessed by dual-energy X-ray absorptiometry (DXA, Hologic QDR 1000/W). RESULTS: Swimmers, who commenced training at 10.7 +/- 3.7 yrs (mean +/- SD) and trained for 24.7 +/- 4.2 hrs per week, had a greater amount of LM (p < 0.05), lower fat mass (p < 0.001) and percent body fat (9.5 vs 16.2%, p < 0.001) than controls. There was no significant difference between groups for regional or total body BMD. In stepwise multiple regression analysis, body weight was a consistent independent predictor of regional and total body BMD. CONCLUSIONS: These results suggest that long-term swimming is not an osteogenic mode of training in college-aged males. This supports our previous findings in young female swimmers who displayed no bone mass benefits despite long-standing athletic training.
Absorptiometry, Photon↗
Falls in older Mexican-American women.
OBJECTIVE: To determine the frequency of falls and identify risk factors for falls among older Mexican-American women. DESIGN: A prospective cohort study with an average follow-up of 2.7 years. SETTING: A clinical center at the Palo Alto Veterans Affairs Medical Center, California. PARTICIPANTS: 152 community-dwelling Mexican-American Caucasian women aged 59 years or older. OUTCOME MEASURES: Falls and injurious falls, as determined by monthly telephone interviews. RESULTS: The rate of falls was 508 per 1000 person-years (95% confidence interval (CI), 440-577). Injurious falls requiring medical attention occurred at a rate of 79 per 1000 person-years (95% CI, 52-107). Factors that were associated independently with an increased risk of falling were older age, a history of arthritis or rheumatism, a history of high thyroid, having fainted at least once in the year before baseline, current use of psychotropic medications, and walking fewer than 5 blocks a day. Those persons with an average time for the chair stand test had a lower risk of falling than those with the slowest times or the fastest times. CONCLUSIONS: The frequency of falls and injurious falls in this cohort of 152 relatively acculturated, healthy, older Mexican-American women was similar or slightly higher than previously reported rates for non-Hispanic Caucasian(s). Many of the factors associated with falls in this study were similar to those reported for non-Hispanic Caucasian women, suggesting that fall prevention measures tested mainly among non-Hispanic Caucasian women would also be appropriate for Mexican-American women.
Accidental Falls↗
Filters and Ayre's T-piece.
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Airway Resistance↗
Effect of muscle strength and movement speed on the biomechanics of rising from a chair in healthy elderly and young women.
The ability to rise from a chair is an important task of daily living that is difficult for many elderly individuals to perform, and is particularly challenging when performed quickly. It is important to understand what factors limit performance of the task in older people, so that effective remedial approaches can be developed. In this study, we quantified lower-extremity muscle strength and chair-rise biomechanics in 12 young and 26 healthy elderly women during chair rise at normal and fast speeds without use of the hands. We found that hip and knee extensor torques, vertical and horizontal momentum, and vertical and horizontal ground reaction forces increased in the same way with speed for all subjects. All subjects increased their speed from normal to fast trials, but the young subjects were able to rise more quickly in the fast trials. In the normal speed trials, elderly subjects generated more trunk flexion and horizontal momentum while still in contact with the chair. Muscle activity patterns were similar for all subjects except that the elderly activated the ankle extensors earlier than the young. Although the elderly subjects were much weaker relative to body weight than the young subjects (48.5+/-14.1%), they were able to generate sufficient torques to perform the task. However, age-related differences suggest that chair-rise biomechanics were affected by the reduction in muscle strength, and that strength training regimes, particularly for the hip musculature, may be important to maintain chair-rise ability in the elderly. Copyright 1998 Elsevier Science B.V.
Journal Article↗
Bone acquisition and loss in children and adults with cystic fibrosis: a longitudinal study.
OBJECTIVES: To determine patterns of bone mineral acquisition in children and young adults with cystic fibrosis (CF) and to identify clinical and laboratory correlates of change in bone mineral density (BMD). STUDY DESIGN: Bone mineral and clinical status were assessed in 41 patients with CF (26 female, aged 9 to 50 years) at baseline and 1.5 years later. Bone mineral content of the lumber spine, femoral neck, and whole body was determined by dual-energy x-ray absorptiometry and expressed as BMD and bone mineral apparent density (BMAD). Changes in weight, height, pubertal status, glucocorticoid use, physical activity, disease severity, and biochemical markers of bone turnover were examined for associations with changes BMD and BMAD. RESULTS: Mean BMD Z-scores (adjusted for age and sex) were reduced at the spine, hip, and whole body at baseline in both adults and youths, and decreased further at all sites among youths at follow-up (-0.4 at spine, p < 0.05; -0.3 at hip, p < 0.10; -0.5 for whole body, p < 0.0005). These data indicate failure to gain bone mineral at the expected rate. BMAD was also reduced at follow-up, suggesting that the observed osteopenia could not be explained by small bone size. Bone loss at multiple sites was observed in four youths and two adults. In general glucocorticoid use, change in body mass, physical activity, and disease severity were the most significant correlates for change in BMD and in BMD Z-score. CONCLUSIONS: Osteopenia in CF generally reflects inadequate gains in bone mineral, although bone loss may occur, particularly in patients requiring glucoc therapy. Late gains in bone mineral may accompany weight gain and pubertal development, but the catch-up appears to be incomplete.
Adolescent↗
Recombinant human growth hormone as potential therapy for osteoporosis.
Growth hormone (GH) directly stimulates proliferation and differentiated functions of cultured bone cells. In addition, temporal relationships between decreased function of the GH/IGF-1 axis and age-related bone loss have prompted some investigators to hypothesize that these two phenomena are causally related, and to test this hypothesis by evaluating the effects of GH administration on bone turnover and mineral density in older men and women. Although these studies show clearly that GH initiates bone remodelling activity, changes in bone mass have not been impressive, even when GH was given in combination with anti-resorptive therapy. Thus, it appears very unlikely that GH will offer a clinically useful means to restore skeletal deficits in patients with osteoporosis.
Aged↗
Prevention of central venous catheter associated thrombosis using minidose warfarin in patients with haematological malignancies.
Thrombosis is a well-recognized complication following insertion of central venous catheters and is associated with significant morbidity. In an attempt to reduce line-associated thrombosis, 108 consecutive patients with haematological malignancies were commenced on prophylactic 'minidose' warfarin, 1 mg/d, at the time of line insertion. This group of patients were compared with a historic group of 115 consecutive patients who had not received warfarin. Clinically-suspected venous thrombosis was confirmed by Doppler ultrasound or venography. Patients taking prophylactic warfarin had their prothrombin time measured three times per week with the aim of maintaining an INR <1.6. Five (5%) of the 108 patients who received minidose warfarin developed a thrombosis, at a median of 72 d (range 5-166) from the time of catheter insertion. In the 115 patients who were not anticoagulated 15 (13%) developed a catheter-associated thrombosis at a median of 16 d (range 1-35). There was a significant reduction in line-associated thrombosis in patients receiving warfarin (P=0.03). These data suggest that minidose warfarin reduces the incidence of central venous catheter related thrombosis in patients with haematological malignancies.
Adult↗
Can a single antibiotic policy for the empirical treatment of febrile neutropenic patients be used for all categories of haematology/oncology patient in the same institution?
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Adult↗
Growth hormone as therapy for older men and women.
Progressive deficits in the growth hormone (GH)/insulin-like growth factor I axis may contribute to the acquired biochemical, body composition, and functional changes of normal human aging, but they do not offer a sole, or even a major explanation for these changes. The concept that GH "replacement" would materially benefit the daily function of older men and women finds little support in the results of the controlled clinical trials that have been reported. GH, either as monotherapy or in combination with antiresorptive medication, does not offer a clinically useful improvement in bone mass, and it is difficult to find a rationale for its use in the treatment of osteoporosis. GH may yet prove to be a useful agent for older men and women in the management of other clinical syndromes, such as visceral obesity, but conclusions in this area await compelling evidence. For the time being, potential benefits of GH in older men and women must be viewed with skepticism, and use of this agent outside the context of a clinical trial is not justified.
Aged↗
CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin's lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin's Lymphoma.
PURPOSE: CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B-cell and T-cell lymphomas. We report here the results of a multicenter phase II trial of CAMPATH-1H in patients with advanced, low-grade non-Hodgkin's lymphoma (NHL) who were previously treated with chemotherapy. PATIENTS AND METHODS: Fifty patients who had relapsed (n=25) after or were resistant (n = 25) to chemotherapy were treated with CAMPATH-1H 30 mg administered as a 2-hour intravenous (i.v.) infusion three times weekly for a maximum period of 12 weeks. RESULTS: Six patients (14%) with B-cell lymphomas achieved a partial remission (PR). Patients with mycosis fungoides appeared to respond more frequently (50%; four of eight patients, which included two complete remissions [CRs]). Lymphoma cells were rapidly eliminated from blood in 16 of 17 patients (94%). CR in the bone marrow was obtained in 32% of the patients. Lymphoma skin lesions disappeared completely in four of 10 patients and partial regression was obtained in three patients. Lymphadenopathy and splenomegaly were normalized in only 5% and 15% of patients, respectively. Lymphopenia (< 0.5 x 10(9)/L) occurred in all patients. World Health Organization (WHO) grade IV neutropenia occurred in 14 patients (28%). Opportunistic infections were diagnosed in seven patients and nine patients had bacterial septicemia. Death related to infectious complications occurred in three patients. CONCLUSION: CAMPATH-1H had a significant but limited activity in patients with advanced, heavily pretreated NHL. The most pronounced effects were noted in the blood and bone marrow and in patients with mycosis fungoides. The risk for serious infectious complications needs to be considered for severely ill patients who are evaluated for CAMPATH-1H treatment.
Adult↗
Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women.
To determine the effects of GH and insulin-like growth factor I (IGF-I) administration, diet, and exercise on weight loss, body composition, basal metabolic rate (BMR), muscle strength, and psychological status, 33 moderately obese postmenopausal women (67.1 +/- 5.2 yr) participated in a 12-week randomized, double blind study. Participants were placed on a diet that provided 500 Cal/day less than that needed for weight maintenance, and they walked 3 days and strength trained 2 days each week. Subjects also self-injected GH (0.025 mg/kg BW.day), IGF-I (0.015 mg/kg BW.day), a combination of these doses of GH and IGF-I, or placebo (P). Twenty-eight women completed the study, as five subjects dropped out due to intolerable side-effects (e.g. edema). Weight loss occurred in all groups, with the largest decrease occurring in the GH plus IGF-I group (5.6 +/- 1.4 kg). Fat mass significantly decreased in all groups, with the largest losses observed in GH and GH plus IGF-I groups (6.3 +/- 1.8 and 8.4 +/- 2.8 kg, respectively). Despite weight loss, BMR was maintained in all groups. Muscle strength increased with training for all groups, and depression and anxiety scores decreased in groups receiving IGF-I. These data show that obese postmenopausal women can lose weight and fat without compromising fat free mass, BMR, or gains in muscle strength, and that GH and IGF-I given together may enhance fat loss over either given alone.
Aged↗
New perspectives on the skeletal role of estrogen.
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Bone Density↗
Exercise: moving in the right direction.
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Adaptation, Physiological↗
Bone mineral, histomorphometry, and body composition in adults with growth hormone receptor deficiency.
Growth hormone (GH) and insulin-like growth factor I (IGF-I) deficiencies have been associated with osteopenia in both children and adults. To examine the effects of growth hormone resistance on bone mineral and body composition, we studied 11 adults (mean age 30 years) with growth hormone receptor deficiency (GHRD, Laron syndrome) and 11 age- and gender-matched controls from Southern Ecuador. Bone mineral and body composition were determined by dual-energy X-ray absorptiometry. Bone physiology was assessed with biochemical markers of bone turnover and dynamic bone histomorphometry. Bone size and body composition differed markedly between subjects with GHRD and controls. Affected adults were 40 cm shorter than controls, had significantly less lean body mass, and had increased percent body fat. Bone mineral content and density (BMD) at the spine, femoral neck, and whole body were significantly lower in adults with GHRD than in controls. Mean BMD Z scores were -1.5 to -1.6 at all sites in affected women and -2.2 to -2.3 in men with GHRD. Estimated volumetric bone density (BMAD) at the spine and femoral neck, however, was not reduced in GHRD. Spine BMAD was 0.210 +/- 0.025 versus 0.177 +/- 0.021 for affected women versus controls (p < 0.05) and 0.173 +/- 0.018 versus 0.191 +/- 0.025 for men with GHRD versus normals (p = 0.31). Urinary pyridinoline concentrations were significantly greater in adults with GHRD than in controls, while type I collagen C-telopeptide breakdown products and markers of bone formation did not differ. Differences in histomorphometry were limited to a reduction in trabecular connectivity; bone volume and formation rate were similar to controls. These data confirm the importance of the GH/IGF axis in regulating bone size and body composition. The contribution of these peptides to the acquisition and maintenance of bone mineral is less certain since volumetric bone density was preserved despite low levels of IGF-I and IGFBP-3 associated with GH resistance.
Absorptiometry, Photon↗