Increments In Bone Mass Research Articles

Osteoporosis

Bone is a dynamic tissue that is remodelled constantly throughout life. The arrangement of compact and cancellous bone provides strength and density suitable for both mobility and protection. Osteoporosis is defined as a reduction in the strength of bone that leads to an increased risk of fractures. The World Health Organisation operationally defined osteoporosis as a bone density also referred to as a T-score of <–2.5 and is associated with increased risk of fractures. Bone remodelling is regulated by multiple hormones, including oestrogens (in both genders), androgens, Vitamin D and parathyroid hormone (PTH), as well as locally produced growth factors, such as IGF-I, transforming growth factor β, PTH-related peptide (PTHrP), interleukins, prostaglandins and members of the tumour necrosis factor superfamily. The risk of fracture can be predicted by the Fracture Risk Assessment score. Several non-invasive techniques are available for estimating skeletal mass or bone mineral density including single energy X-ray absorptiometry, dual-energy X-ray absorptiometry, quantitative computed tomography and ultra-sound. Total daily calcium intakes <400 mg are detrimental to the skeleton. The recommended daily required intake of 1000–1200 mg for adults accommodates population heterogeneity in controlling calcium balance. For optimal skeletal health, serum 25(OH)D should be >75 nmol/L (30 ng/mL). Bisphosphonates have become the mainstay of osteoporosis treatment. Calcitonin preparations are approved by the FDA for osteoporosis in women >5 years past menopause. Denosumab was approved by the FDA in 2010. Parathormone analogues augment trabecular bone mineral density and reduce fracture occurrence. PTH (1–34) (teriparatide) produced substantial increments in bone mass. Abaloparatide is a synthetic analogue of human PTHrP, which has significant homology to PTH and also binds the PTH Type 1 receptor increasing the bone mass. Ageing is associated with progressive decline in overall muscle strength and bone loss. Resistance training increases bone strength and density, reducing the risk of fracture during a fall. Increased levels of endurance, strength and balance with exercises increase the threshold for disability and dependence as we age. Inactive and sedentary lifestyle should be discouraged. Treatment accessibility could be improved and treatment adherence should be encouraged.

Alendronate versus Raloxifene for Postmenopausal Women: A Meta-Analysis of Seven Head-to-Head Randomized Controlled Trials

Purpose. The aim of this study was to directly compare the efficacy and the safety of the two agents for postmenopausal women. Methods/Principal Findings. Electronic databases were searched for relevant articles that met our predefined inclusion criteria. Seven randomized controlled trials (RCTs) involving 4054 women were identified and included. Although Aln was more effective than Rlx in increasing bone mineral density (BMD), no statistical differences were observed in reducing the risk of neither vertebral fractures (P = 0.45) nor nonvertebral fractures (P = 0.87) up to two-year followup. Aln reduced the risk of vasomotor (P = 0.006) but increased the risk of diarrhea compared to Rlx (P = 0.01). Our subgroup analysis further indicated the difference between Aln and Rlx in fracture risk and was not materially altered by the administration pattern, the age. The weekly strategy of Aln would further reduce the upper gastrointestinal (GI) disorders and might gain more bone mass increment at lumbar spine compared to its daily treatment. Conclusion. There was no evidence of difference of fracture risk reduction between Aln and Rlx. In addition, age did not obviously influence their relative antifracture efficacy. For Aln the weekly strategy would further reduce the upper GI disorders and gain more bone mass increment compared to the daily treatment. During clinical decision making, the patients' adherence and the related side-effects associated with both drugs should also be taken into account.

Strengthening the bones in primary biliary cirrhosis

Strengthening the bones in primary biliary cirrhosis

Bone Geometry According to Menstrual Function in Female Endurance Athletes

Athletes have higher bone mineral density (BMD) relative to nonathletes. In amenorrheic athletes BMD may be compromised by estrogen deficiency, but it is unknown whether this is accompanied by structural differences. We compared femoral neck bone geometry and density of a-/oligomenorrheic athletes (AAs), eumenorrheic athletes (EAs), and eumenorrheic controls (ECs). We recruited 156 women: (68 endurance athletes and 88 controls). Femoral neck BMD, section modulus (Z), and width were measured using dual-energy X-ray absorptiometry. Menstrual function was assessed by questionnaire and classified as EA (≥10 periods/year) or AA (≤9 periods/year): 24 athletes were AA and 44 EA. Femoral neck BMD was significantly higher in EA than AA (8 %, difference) and EC (11 % difference): mean [SE] 1.118 [0.015], 1.023 [0.020] and 0.999 [0.014] g cm(-2), respectively; p < 0.001. Z was significantly higher in EA than EC (11 % difference): EA 667 [19], AA 625 [21], and EC 592 [10] cm(3); p < 0.001. Femoral neck width did not differ between groups. All differences persisted after adjustment for height, age, and body mass. The higher femoral neck Z and BMD in athletes, despite similar width, may indicate that exercise-related bone gains are endosteal rather than periosteal. Athletes with amenorrhea had smaller increments in bone mass rather than structural adaptation. The maintained femoral neck width in controls may be an adaptive mechanism to conserve bone strength in bending despite inactivity-related bone decrement.

Bora Bora therapy for osteoporosis

Objective: to have an analgesic effect, to improve spinal mobility, and to maintain adequate bone mineral density (BMD) in patients with osteoporosis (OP) treated with Bora Bora that has a combined effect on bone tissue. Subjects and methods. Fifteen patients (mean age 63,7+8,4 years) with OP were treated with Bora Bora as a capsule 4 times daily for 6 months. During Bora Bora treatment, another therapy for OP was not performed. The intermittent use of nonsteroidal anti-inflammatory drugs (NSAIDs) was allowed in severe pains. The patients underwent a routine clinical laboratory examination; dual-energy X-ray absorptiometry (DEXA) was used to estimate BMD; the authors determined the intensity of pain in the back and on palpation of paravertebral muscles by the VAS (visual analog scale (in mm), the range of spinal motions, the overall efficiency of treatment, and the presence of adverse reactions. Examinations were made on the day of treatment initiation, following 2 weeks, and at months 1, 2, 3, and 6 of Bora Bora therapy. Results. Increased BMD was noted in all the patients after treatment with Bora Bora (according to the data of DEXA). The effect depended on the timeliness of using the drug. The rate of BMD increase in the lumbar vertebrae was 0,5-2% higher than that in the femoral neck in 50- 70-year-old women. After 70 years of age, the rate of a bone mass increment was much less, particularly in the femoral neck. Conclusion. When Bora Bora was given, there was pain relief and increases in the range of vertebral motions and BMD. Bora Bora was shown to be well tolerated by and to be beneficial to patients with OP.

Connexin43 Modulation of Osteoblast/Osteocyte Apoptosis: A Potential Therapeutic Target?

Connexin43 Modulation of Osteoblast/Osteocyte Apoptosis: A Potential Therapeutic Target?

Improvement of bone health in childhood and adolescence.

Osteoporosis as a worldwide problem is discussed in the present review and the question of improving peak bone mass to reduce the risk of osteoporosis and osteoporotic fracture is addressed. The available evidence points to pre-puberty and puberty as the most opportune periods for intervention, but the potential for achievable increments in bone mass is shown to be small compared with the overwhelming influence of heredity, body composition and hormonal factors on bone. Lean body mass appears to be positively correlated with bone mass, while black-white racial differences in bone mass appear to be related to greater lean mass and lower bone turnover rate in blacks. Within races, twin and parent-offspring models have suggested that 46-80 % of the variance in bone mineral density can be explained by inherited factors; however, the mechanism of the genetic influence on bone density remains poorly understood. Moderate regular exercise seems to maintain bone mass while more vigorous regular exercise increases it in children and young adults. Ca intake has been found to be positively associated with bone mass in many but not all studies, possibly because of a ceiling at about 1300-1500 mg/d for young people. Other nutritional variables, including vitamin D, have been little investigated in relation to childhood and adolescent bone mass. The influence of milk as a source of highly bioavailable Ca and other nutrients has also been less frequently investigated, which is of concern given the cessation of school milk programmes in Western countries over the last three decades. Intervention studies to improve bone health in young people have mainly been based on Ca milk or exercise. The evidence points to the benefits to bone of such interventions, particularly when commenced pre-puberty, and it seems that daily consumption of 200-300 ml milk/d by children and adolescents has no adverse side effects. The benefits to bone are almost universally shown to be lost fairly rapidly after Ca or exercise intervention ceases; there is therefore no justification in terms of bone health for short-term interventions of this nature. The question of withdrawal of milk supplementation has undergone very little examination. Further, very little evidence is available on the effects of long-term interventions of any sort on bone health. Nevertheless, the data obtained so far permit the suggestion that promotion of Ca intake (e.g. at the higher level of current recommendations) and exercise commencing in the pre-pubertal period should be adopted as policy now.

Parathyroid and bone. Role of parathyroid hormone in the treatment of osteoporosis

Parathyroid hormone (PTH) , a potent anabolic agent, produces larger increments in bone mass than those seen with antiresorptive agents. No further benefit is expected in PTH and antiresorptive combinations in treatment-naïve patients of osteoporosis, but in cases achieving the plateau level of BMD with established alendronate PTH can stimulate bone formation and increase BMD again. Alendronate treatment after PTH therapy can maintain gains in BMD at lumbar spine and hip as well. Many possibilities are expected in the role of PTH therapy in osteoporosis treatment.

A Clinical Trial of 3 Doses of Transdermal 17β-estradiol for Preventing Postmenopausal Bone Loss: A Preliminary Study

It is well documented that a daily oral dose of 0.625 mg of conjugated equine estrogen or 1-2 mg of 17beta-estradiol is needed to prevent postmenopausal bone loss. Recent studies have indicated that a lower dose of estrogen maybe as effective in maintaining bone mass. The purpose of this study was to evaluate the effects of 3 dosages of transdermally administered 17beta-estradiol gel in postmenopausal women stratified by oophorectomy and natural menopause. One hundred and twenty postmenopausal women were randomly selected to form 4 groups. Three groups of women were treated with a transdermal administration of estradiol gel at a daily dosage of 1.25, 2.5 and 5.0 g (containing 0.75, 1.5, and 3 mg of 17beta-estradiol/day), respectively. The 4th group of women, receiving estriol 2 mg/day p.o., was studied concurrently as a control. Bone mineral density was measured by quantitative computed tomography of the vertebrae from T12 to L3 at baseline, then at 6-month intervals for 1 year. Women in all groups receiving 17beta-estradiol gel obtained a significant increase in bone mass, with the exception of the 1.25 g/day group, which showed a minimal increment at the 6-month period, compared with the control group. Comparisons of the increments in bone mass after estrogen therapy for both natural and surgical menopausal subjects found that there was a more prominent response in surgical menopausal women receiving a dosage of 2.5 g/day. Estradiol gel at the dosage of 1.25 g/day, equivalent to 17beta-estradiol 0.75 mg/day, effectively prevented bone loss in postmenopausal women after a 12-month treatment period. The therapeutic effect of estradiol gel on bone mass was more prominent in the surgical menopausal groups at the dosage of 2.5 g/day. The atrophic ovaries may therefore play a crucial role in the subsequent decades of postmenopausal women.

A cross-sectional study of smoking and bone mineral density in premenopausal parous women: effect of body mass index, breastfeeding, and sports participation.

The objective of this cross-sectional study was to describe the relationship between cigarette smoking, effect modifiers, and bone density in premenopausal parous women. We studied a sample of 276 women (mean age 33 years) from Southern Tasmania. The study factors were cigarette smoking, body mass index (BMI), sports participation, and breastfeeding history. Bone mineral density was measured utilizing an Hologic QDR 2000 densitometer and converted to Z scores using the group mean and variance. There were 118 current smokers and 158 nonsmokers. Smokers had lower bone mass at all sites (femoral neck, -0.32 SD, 95% confidence interval [CI] -0.60 to -0. 04; lumbar spine, -0.49 SD, 95% CI -0.76 to -0.22; total body, -0.40 SD, 95% CI -0.66 to -0.14). Stratifying by BMI revealed that this association was only present, but greater in magnitude, for those with a BMI <25 kg/m2. Smokers who had breastfed at least one child had an additional deficit in bone mass (femoral neck, -0.48 SD, 95% CI -0.89 to -0.07; lumbar spine, -0.39 SD, 95% CI -0.80 to 0.02; total body, -0.37 SD, 95% CI -0.77 to 0.06) while smokers who took part in competitive sport had significant increments in bone mass (femoral neck, 0.74 SD, 95% CI 0.31 to 1.17; lumbar spine, 0.48 SD, 95% CI 0.03 to 0.93; total body, 0.42 SD, 95% CI 0.00 to 0.84). Neither of these two associations were present in nonsmokers. In conclusion, current smoking was associated with substantial deficits in bone mass in our sample of women, particularly those with a BMI <25 kg/m2. In addition, smoking may prevent the usual postweaning recovery phase of bone after breastfeeding while sports participation may offset the negative effect of smoking on bone mass. These observations need to be confirmed in longitudinal studies but they imply that past studies of smoking in this age group may have missed important associations as they did not consider possible effect modifiers.

Longitudinal changes in bone density in hyperparathyroidism.

Primary hyperparathyroidism (HPTH) is a known risk factor for cortical bone loss. The primary objective of this study was to examine the time course and location of changes in bone mass within the first year after parathyroidectomy (PAX). The secondary goal was to evaluate the efficacy of combined estrogen therapy and parathyroidectomy in postmenopausal women. Thirty-two subjects with primary HPTH participated in a prospective, longitudinal study for at least 1 yr. Twenty-seven subjects underwent PTX, while five received no therapy (control). Among the PTX patients, 21 were postmenopausal women, and 8 of these women also received estrogen. Subjects had serial measurements of parathyroid hormone levels, serum chemistries, and bone density at multiple sites. Among all PTX patients, lumbar spine, hip, and whole body bone mineral content increased significantly (3.8-6%; p < 0.005) at 12 mo, with most of the increments observed by 3 mo. In postmenopausal women, estrogen treatment resulted in higher increments in the femoral neck (8.6 +/- 2% vs 4.9 +/- 1.2%, respectively; p = 0.07) and the whole body (6 +/- 2% vs 2.4 +/- 1.6%, respectively; p = 0.07). In HPTH, early and generalized increments in bone mass follow PTX, and the combination of surgery with estrogen therapy may be superior to surgery without estrogen treatment. A randomized, controlled trial including PTX, estrogen, and a combination of the two is needed to determine the optimal therapy in postmenopausal women.

Axial and peripheral bone mineral acquisition: a 3-year longitudinal study in Chinese adolescents.

We performed a 3-year longitudinal study of a group of 179 healthy Chinese adolescents (92 boys and 87 girls) aged from 12 to 16 years to determine the effects of puberty, physical activity, physical fitness, and calcium intake on the acquisition of bone mass. At yearly intervals for 3 consecutive years we recorded nutrition, calcium intake and anthropometric measurements, and assessed pubertal status according to Tanner. Bone mass of the lumbar spine was determined by dual-energy X-ray absorptiometry and radial bone mass by single-photon absorptiometry. Physical fitness and level of physical activity were assessed and muscle strength and power determined by isokinetic testing. Peripheral bone mass correlated with axial skeleton bone mass. Age, pubertal staging, physical fitness and muscle strength were significantly associated with bone mass increments on cross-sectional univariate and regression analysis. Longitudinal regression analysis showed that the most important factor affecting bone mass accretion in adolescents in both sexes was their pubertal stage. In boys, bone mass increment throughout the study was greater in children who were already in the advanced pubertal stages on entering the study than in those who started puberty in year 2 or 3 of the study. The percentage change in bone mineral content of the forearm and in bone mineral density of the lumbar spine was greater than 25% in the advanced pubertal group as compared to around 20% in the less mature group. For girls, the reverse was true. The increment of bone mass during the study period was significantly greater in those who presented in the earlier pubertal stages than in those who were at the more advanced stage of puberty on entry into the study. There was no significant effect of calcium intake and physical activities on the bone mass accretion. In Chinese adolescents, bone mineral accretion at adolescence is not influenced by exercise, level of physical fitness and calcium intake. In both sexes, and especially in girls, to optimally increase bone mass, regular physical exercise programmes should be instituted well before the onset of puberty rather than at or after it. Once puberty starts, these interventions may have no or only limited effect.

Role of soy protein with normal or reduced isoflavone content in reversing bone loss induced by ovarian hormone deficiency in rats

Soy protein, a rich source of isoflavones, fed immediately after an ovariectomy prevents bone loss in rats. Reports of the effectiveness of natural and synthetic isoflavones in preventing or treating osteoporosis led us to examine the effect of soy protein in reversing established bone loss. Seventy-two 95-d-old female Sprague-Dawley rats were assigned to 6 groups. The rats were either sham operated (SHAM; 2 groups) or ovariectomized (OVX; 4 groups) and then fed a casein-based, semipurified diet. Thirty-five days after surgery, 1 SHAM and 1 OVX group were killed to examine the occurrence of bone loss. Thereafter, the other SHAM and 1 OVX groups continued to receive the casein-based diet. Whereas the remaining 2 OVX groups received diets in which casein was replaced by soy protein with normal (OVX+SOY) or reduced (OVX+SOY-) isoflavone content for 65 days. The OVX control group had significantly lower femoral and fourth lumbar vertebral bone densities than the SHAM group. Femoral density of rats fed SOY or SOY- diets were not significantly different from SHAM or OVX controls. This suggests a slight reversal of cortical bone loss that may be partially due to higher femoral insulin-like growth factor I mRNA transcripts resulting from both the SOY and SOY- diets. The ovariectomy-induced increases in indexes of bone turnover were not ameliorated by either of the soy diets, suggesting that any positive effect of soy was achieved through enhanced bone formation rather than slowed bone resorption. Long-term consumption of soy or its isoflavones may be needed to produce small but continued increments in bone mass.

Rationale for the use of alendronate in osteoporosis.

Bisphosphonates are being used in disorders associated with accelerated resorption of bone, particularly Paget's disease of bone and the bone disease of malignancy. Their undoubted biological efficacy and relatively low apparent toxicity make them attractive candidates for the management of osteoporosis. The bisphosphonate alendronate has many characteristics which suggest that it is suitable for use in osteoporosis. It is a potent inhibitor of osteoclast-mediated bone resorption with no adverse effect on the mineralization of bone. Earlier studies have shown it to be one of the most active bisphosphonates in Paget's disease and the hypercalcemia of malignancy. In common with other bisphosphonates tested thus far, alendronate appears to inhibit bone loss in a variety of experimental models of osteoporosis. Long-term studies are needed to determine its steady-state effects on bone mass in man. Most data indicate that alendronate is capable at least of decreasing the rate of bone loss, and might even induce increments in bone mass for many years. Since the experimental studies show that the increase in bone mass observed with alendronate is associated with an increase in bone strength, its use is likely to decrease the frequency of fractures. However, direct clinical evidence for this requires the outcome of well-designed long-term prospective studies.

Estrogen in Prevention and Treatment of Osteoporosisa

Estrogen has clearly been shown to decrease bone loss and frequency of osteoporotic fractures. Calcitonin has been shown in several studies to reduce the rate of bone loss, although no data are yet available demonstrating a reduction in fracture frequency. Studies of osteoporosis intrinsically assume that prevention of further loss, or increments in bone mass, will be associated with declines in fracture recurrence. That may not always be the case. Recent controlled studies in which fluoride was used to increase bone mass in vertebral bodies resulted in no significant decline in fracture recurrence, and there was even a suggestion of increased fracture risk at some sites. Thus further data on calcitonin will be important, even though calcitonin is not expected to alter bone quality as does fluoride. Alternative therapies to calcitonin and estrogen are being investigated in clinical studies since both are currently limited in their use. Because calcitonin currently requires nearly daily injections, estrogen remains the principal agent available for both prevention and treatment in spite of its wide effect on multiple body systems. Bisphosphonates, given continuously or intermittently, appear to be relatively safe oral alternatives to calcitonin. The long-term effects of these agents need to be evaluated in greater detail before they can be recommended for prevention, but a role in therapy of the established disorder seems likely. The skeletal effect of bisphosphonates is also inhibition of bone remodeling and therefore prevention of further bone loss. Thus, they add nothing to the other therapeutic regimens from this perspective and as with calcitonin therapy, documentation of decreased frequency of fracture is lacking. Agents to increase bone mass are purely investigational at this time and many years may elapse before efficacy can be shown for such interventions.

Treatment of osteoporosis with calcitonin, with and without growth hormone

A 24 month randomized parallel study of the treatment of postmenopausal osteoporosis with calcitonin alone v calcitonin alternating with growth hormone (combined treatment) was conducted. Each group received 1000 mg daily of oral calcium supplements. The rate of change in total body calcium for the combined and calcitonin groups was +1.68%/yr and +1.33/yr, respectively ( P < .05). However, the difference in the two groups was not statistically significant. Further, the total body calcium level did not increase after 12 to 18 months of treatment. There was a significant difference in the rates of change of bone mineral content (BMC) of the radius for the two groups, with a loss of BMC in the combined treatment group ( F = 4.80, P < .05). Calcitonin treatment is effective in producing an increment in bone mass. The addition of growth hormone to this regimen appears to have a deleterious effect on cortical bone mass.

Monofluorophosphate Physiology: The Effects of Fluoride on Bone

Fluoride is an effective agent in the treatment of osteoporosis and is the only available agent that is capable of producing a large increment in bone mass. Fluoride stimulates bone formation largely through its action to increase osteoblast number. In vitro work suggests that the effect of fluoride to increase osteoblast number is due to a direct action of fluoride to stimulate the proliferation of osteoblast precursors. In fluoride-treated patients the increase in bone formation leads to an increase in bone mass as manifested by an increase in X-ray density, which in turn leads to a decrease in bone pain and a decrease in fracture rate. These positive effects are limited to the axial skeleton and are not observed in the appendicular skeleton in the dose used. The increase in bone formation is reflected by an increase in serum total alkaline phoshatase activity, which is due to an increase in the bone isoenzyme and which can be used to assess serially the action of fluoride on bone. Serum total alkaline phosphatase activity measurements indicate that, during 2 years of fluoride treatment, about 80% of patients respond and that the magnitude of the response is quite variable. The major disadvantages of fluoride in the treatment of osteoporosis include: (1) All patients do not exhibit a response. (2) Fluoride treatment causes gastric and joint side effects in a significant proportion of patients.

Changes in body composition following therapy of osteoporosis with methandrostenolone

A two compartment, double-blind, randomized, parallel study was performed comparing methandrostenolone with placebo in the treatment of osteoporosis. The duration of the study was 24 mo. Dependent parameters included total body calcium (TBCa), measured by neutron activation analysis; bone mineral content of the radius (BMC), measured by photon absorptiometry; and total body potassium (TBK), measured by total body counting. A significant increase in TBK occurred in the treated group, primarily in the first 6 mo; thereafter the TBK remained fairly constant. No significant changes in bone mass occurred, except the 6 mo TBCa measurement increased by 11 grams for the methandrostenolone group and decreased by 6 grams for the placebo group ( p = .05). Other evidence also suggests that anabolic steroids may not produce sustained uncoupling of bone formation and bone resorption in osteoporosis. If methandrostenolone is capable of producing an increment in bone mass in osteoporosis, it was not readily observable with the sensitivity of the techniques employed in this study.

Exercise and skeletal health.

Involutional osteopenia contributes to older persons' susceptibility to fractures of the hip, spine and wrist. Experimental evidence is reviewed that supports the hypothesis that involutional bone loss can be prevented by physical exercise. Weightlessness and immobilization result in accelerated bone loss. In cross-sectional studies measuring total body potassium (TBK), both muscle mass and bone mass in normal humans have remained strikingly constant. The usual decrease in total body calcium (TBCa) and TBK with increasing age was not observed in a cross-sectional study of marathon runners. Localized hypertrophy of bone and muscle has been reported for a variety of occupations and sports. Two prospective studies have demonstrated an increment in bone mass after a program of physical exercise. It would seem that certain involutional changes in body composition (loss of TBCa and TBK) can be prevented by increased physical activity, but the effectiveness of specific types and durations of exercise should be investigated.