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Influence of weight and body fat distribution on bone density in postmenopausal women.

OBJECTIVE: To determine whether obesity or body fat distribution induces a greater modification on bone remodeling biochemistry (BRB) and bone density in postmenopausal women. METHODS: One hundred and thirteen postmenopausal patients were studied. They were initially divided according to body mass index (BMI), and afterwards by waist-hip ratio (WHR) as well as combinations of the two factors. Hormone measurements and assessments of BRB were also done. Dual-emission X-ray absorptiometry from the lumbar column and hip was performed with Lunar DPXL equipment, and the standard deviation in relation to young adult (T) and age-matched subjects (Z) was calculated. Statistical analysis was done by the Mann-Whitney U test. The relation of BMI and WHR with the variables was calculated by simple regression analysis. RESULTS: When divided according to BMI, there was greater bone density in the femoral neck in those with normal weight. After dividing according to WHR, the Z scores had a trend to a lesser decrease in those with upper level body fat distribution. Divided according to BMI and WHR, obese patients with upper-level body fat distribution had greater bone density in the lumbar column than those with normal weight and lower-level body fat distribution. With the same WHR, those with normal weight had greater bone density than those who were obese. CONCLUSIONS: A beneficial effect of upper-level body fat distribution on bone density was found. It is greater than that from obesity alone, and obesity and upper-level body fat distribution have an additive effect on bone density.

Adipose Tissue↗

Bone density interpretation and relevance in Caucasian children aged 9-17 years of age: insights from a population-based fracture study.

The interpretation of bone density measurement in children is difficult due to a number of factors including rapid change in body size and uncertain clinical significance of bone density in children. This study asked two questions. (1) Is there a preferred bone density measurement site or type for fracture risk in children? (2) What is the best way to interpret bone density in children? This population-based case control study included 321 upper limb fracture cases and 321 class- and sex- matched randomly selected controls. Bone density at the hip, spine, and total body (including the arm) was measured by a Hologic QDR2000 densitometer (Waltham, MA) and examined as bone area (BA), bone mineral content (BMC), bone mineral density (BMD), bone mineral apparent density (BMAD), and BMC/lean mass (BMCLM). The only dual-energy X-ray absorptiometry (DXA) variables that were consistently associated with fracture risk in both boys and girls were spine BMD and BMAD for total upper limb fractures, and spine and hip BMAD for wrist and forearm fractures. No significant associations were observed for BA and BMCLM and inconsistent associations for BMC and other BMD sites. Five-yr fracture risk varied from 15-24% depending on site and gender in a child with a Z-score of -3. In the controls, all DXA variables were associated with age, height, and weight, but the weakest associations were with BMAD. In conclusion, in this study the spine BMAD had the strongest and most consistent association with upper limb fracture risk in children. The associations with age and body size imply that age specific Z-scores will be the most convenient for interpretation of DXA measures in children. Five-yr wrist and forearm fracture risk has potential as a clinical endpoint of immediate relevance.

Absorptiometry, Photon↗

Exercise-associated amenorrhea, low bone density, and estrogen replacement therapy.

BACKGROUND: Women with exercise-associated amenorrhea have a higher frequency of osteoporosis than eumenorrheic runners and sedentary women. The use of hormone replacement therapy was suggested many years ago to increase bone density in exercising women with amenorrhea and low bone density. OBJECTIVE: To determine if hormone replacement therapy increased bone density in women with exercise-associated amenorrhea. METHODS: We performed a retrospective clinical study comparing the changes in bone density in 8 women runners who took hormone replacement therapy with 5 who refused medication but who were followed up as controls over 24 to 30 months. RESULTS: Vertebral and femoral neck bone density significantly increased by 8.0% +/- 1.2% (+/- SEM) and 4.1% +/- 0.3% (+/- SEM), respectively, in 8 women runners with amenorrhea taking 24 to 30 months of estrogen replacement therapy with progestational support. Control women not taking replacement therapy had nonsignificant decreases of less than 2.5% at each site. CONCLUSION: Hormone replacement therapy appears to increase bone density in amenorrheic runners.

Adult↗

Longitudinal study of bone density and its determinants in women in peri- or early menopause.

The evolution of bone mass across menopause as well as the factors related to bone loss were studied in 141 women already assessed 10 years ago while in premenopause. Bone density of the lumbar spine was measured by dual photon absorptiometry. Nutrient intakes, lifestyle habits, data on menopause, and hormone replacement therapy were obtained by questionnaires. Present bone density was related significantly to past and current calcium intake, current vitamin D intake, and leisure physical activity level, as well as bone density measured in premenopause. Average bone loss was related to time elapsed without estrogens, age at menopause and present age, as well as serum levels of osteocalcin and alkaline phosphatase (ALP). Bone loss was inversely related to calcium and vitamin D intakes and to serum 25-OH vitamin D (25OHD) levels. By multiple regression analyses, only bone density in premenopause, time without estrogens, weight, vitamin D intake, and serum ALP levels remained as independent predictors of present bone mass or bone loss. This study emphasizes the importance of building a good bone mass before menopause, of having adequate vitamin D intake, and of beginning estrogen replacement therapy as soon as possible to minimize bone loss in the first years of menopause.

Adult↗

Determinants of peak trabecular bone density in women: the role of androgens, estrogen, and exercise.

To elucidate determinants of peak trabecular bone density, we studied the role of androgens, estrogen, and aerobic exercise in 30 women from 18 to 22 years old. The women were divided into three groups: Sedentary, 11 normal women who did not exercise regularly; eumenorrheic, 10 athletes with normal menstrual function; and oligomenorrheic, 9 athletes with exercise-induced oligomenorrhea. All athletes participated in aerobic sports that did not involve selective resistance loading of the back. Serum free and albumin-bound testosterone (fab T), androstenedione (A), and estradiol (E2) were measured on four separate occasions at consecutive 7 day intervals and averaged. Trabecular density was measured by quantitative computed tomography of the lumbar spine. Peak trabecular bone density was related to fab T (r = 0.48, p = 0.007), A (r = 0.40, p = 0.03), and E2 (r = 0.40, p = 0.04). When taken in combination, androgens and estrogen each accounted independently for significant portions of the variance in bone density [fab T and E2 (R2 = 0.38, p = 0.002) and A and E2 (R2 = 0.27, p = 0.01)]. Bone density (mg/ml, mean +/- standard error of the mean, SEM) in the sedentary group (174 +/- 6) was not significantly different from that in the eumenorrheic (183 +/- 12, p = 0.47) or oligomenorrheic (161 +/- 11, p = 0.32) subjects. We conclude that androgens and estrogen function as independent and additive determinants of peak trabecular bone density in young women. The quantitative impact of aerobic exercise (without resistance loading) and exercise-induced menstrual dysfunction appears to be less important than that of the hormones.

Adolescent↗

Skeletal challenge: an experimental study of pharmacologically induced changes in bone density in the distal radius, using gamma-ray computed tomography.

Bone density (BD) at the distal end of the radius was measured serially with gamma-ray computed tomography (gamma-CT) in five groups of healthy postmenopausal women. One group comprised untreated controls; women in the other groups were subjected to pharmacologic challenge with putative activators and/or depressors of bone remodeling. The challenge agents, taken orally, were ergocalciferol (vitamin D2) alone and followed by calcium; calcitriol (1,25(OH)2D3), and prednisone. All of the subjects showed changes in BD following challenge; these changes were significant (P less than 0.05) for the groups receiving vitamin D2 and vitamin D2 plus calcium. Responses to ergocalciferol, calcitriol, and prednisone were similar within groups, whereas the group receiving ergocalciferol then calcium comprised two distinct subgroups: bone density transiently increased in one and decreased in the other. For all five groups, the direction of change in bone density in response to the challenge, and its duration and magnitude, were consistent with reported histomorphometric data. We conclude that gamma-CT assessment of change in bone density after pharmacologic challenge provides a useful noninvasive approach to skeletal investigation.

Aged↗

[Lumbar bone density. Risk factor for vertebral fractures in women].

BACKGROUND AND OBJECTIVE: The direct connections between a reduction in bone density and an increase in the incidence of fractures with increasing age is well known. When interpreting bone density measurements the attending physician is confronted with an overlap of false-positive and false-negative parameters, as is also the case with biochemical data. Aim of this study was to determine, in addition to bone density, a fracture threshold, i.e. a value for bone density with maximal sensitivity and specificity, in a representative cohort of women. PATIENTS AND METHODS: 534 healthy women (mean age 60.9 +/- 8.07, range 40-83 years), seen in an out-patient osteological clinic between 1993 and 1996 were included. After full biochemical investigation to exclude a metabolic bone disease, bone density (LBD) of the lumbar vertebrae 1-5 and the number of vertebral body fractures were documented, together with age and menopausal status. LBD was measured by quantitative computed tomography (qCT), results being analysed with the Wilcoxon 2-sample test and logistic regression and assessed by receiver operating characteristics (ROC) analysis. RESULTS: None of the women with a qCT value over 111 mg/cc had evidence of vertebral fractures. Those with values under 60 mg/cc had at least one vertebral fracture (defined as at least 15% reduction in vertebral body height). There was a highly significant negative correlation between age and LBD (r = -0.56; P < 0.0001), as well as between LBD and the number of fractured vertebrae (r = -0.58, P < 0.0001). But there was no longer any correlation between age and number of vertebral body fractures once allowance was made for LBD (r = 0.001, not significant). The least overlap of false-positive and false-negative values was at an LBD with qCT values of 102 mg/cc. CONCLUSIONS: LBD is the determining variable for fracture risk independent of age. Despite an overlap of false-positive and false-negative LBD values, the probability of fractures can be predicted from bone mineral content.

Adult↗

Bone density: is it affected by orchidectomy and radiotherapy given for stage I seminoma of the testis?

A cross-sectional study of bone density involving 30 patients who had undergone orchidectomy and para-aortic radiotherapy for Stage I seminoma of the testis, has been performed. Bone density measurements were made of the whole body, lumbar spine and hips, including all irradiated areas. Comparison was made with previously obtained standard sex and age matched control data. The 30 patients treated for seminoma had a significantly increased mean bone density compared with age matched normal values. No significant differences were demonstrated between the mean bone densities of the irradiated and non-irradiated hips. There was no significant relationship between bone density measurement and time since orchidectomy or radiotherapy. These results suggest that nodal irradiation for seminoma has little long term effect on bone density.

Absorptiometry, Photon↗

Secondary hyperparathyroidism is associated with vitamin D receptor polymorphism and bone density after renal transplantation.

Immunosuppresive treatment and secondary hyperparathyroidism (SHPT) are considered among the most important pathogenetic factors for post-renal transplant bone disease. The aim of this study was to investigate the relationships among vitamin D receptor (VDR) gene polymorphism, parathyroid hormone (PTH) levels and bone density in renal transplant recipients. We enrolled 75 patients (50 male and 25 female, mean age 47+/-11 years) who had undergone kidney transplantation 53+/-4 months before. All patients underwent an evaluation of the main biochemical parameters of bone metabolism as well bone densitometry. VDR alleles were typed by a PCR assay based on a polymorphic BsmI restriction site. When patients were categorized according to the VDR genotype (BB, Bb, bb), serum creatinine and the cumulative doses of immunosuppressive drugs were similar across the groups. PTH levels higher than 80 pg/ml were found in 53.6% of the patients, with the highest values being detected in the bb VDR genotype (P<0.05). PTH was significantly correlated to urinary NTx values. Bone density was low in the whole population; however, spinal bone density was lower in the bb subgroup (P<0.02). In the whole population, only PTH (P<0.05) and body mass index (P<0.01) were independent predictors of spinal bone density. Grouping patients by the VDR gene polymorphism, only PTH continued to be an independent predictor of spinal bone density in the bb allele subgroup (R(2) Adj.=0.17). We can conclude that the VDR genotype polymorphism affects bone density of renal transplant recipients via its effects on the severity of SHPT.

Adult↗

[Measuring bone density with ultrasound--ready for general practice?].

Osteoporosis is characterized by low bone mass, loss of bone structure and/or typical fractures (vertebrae, radius, hip). The costs for the treatment of hip fractures in Germany are about 1 billion DM per year, the mortality rate after hip fractures is between 10 and 30% within the first year. Low bone mass is an important risk factor for the development of fractures; so far however, no procedure for the measurement of bone density has been able to 100 percent differentiate between patients with established osteoporosis and healthy people of the same age. This is due to the fact that the defect in bone structure causing the disease could not be measured so far. Quantitative ultrasonometry (QUS) is a new, non-invasive, radiation-free method for the in vivo measurement of bone density and bone structure. Measurements at the calcaneus and at the phalanxes have shown the equivalence of QUS compared to radiological methods in prospective studies with regard to the prediction of hip fractures. Furthermore it was shown that the beneficial osseous effects of postmenopausal estrogen/gestagen replacement therapy can be detected by QUS. Since QUS is considerably cheaper and the devices are easily transportable, this method is a valuable supplement in the range of diagnostic tools in osteology. Its clinical value however depends on the experience of the user and it should be applied in patients only together with medical history, physical examination and perhaps additional imaging procedures. It was not the inadequate methodology that has brought osteodensitometric methods into discredit but the undifferentiated handling by inexperienced users.

Bone Density↗

Intravenous pamidronate attenuates bone density loss after acute spinal cord injury.

OBJECTIVE: To compare the effects of a 6-month treatment with intravenous pamidronate (30-mg infusion once per month) to conventional rehabilitation without pamidronate on bone density of the spine and leg bones and on the excretion rate of N-telopeptide, a urinary marker of bone catabolism, in acutely spinal cord injured patients. DESIGN: A nonrandomized control trial in which 24 spinal cord injured subjects entered the study within 6 weeks of their injury. Fourteen subjects received pamidronate; 10 did not. OUTCOME MEASURES: Bone density measurements by dual x-ray absorptiometry were performed before the initial treatment (within 6 weeks of the injury) and at 3, 6, and 12 months postinjury and was the primary efficacy parameter. Urine for N-telopeptide levels was the secondary efficacy parameter. RESULTS: After acute spinal cord injury, patients treated with intravenous pamidronate had significantly less bone density loss compared with those who did not receive pamidronate (parametric ANOVA, p<.02). Also, ambulatory subjects had significantly less bone density loss over the study period (p<.05) than nonambulatory subjects. In general, a high excretion level of the urinary bone-breakdown product N-telopeptide was found before intravenous pamidronate treatment, followed by a dramatic reduction in excretion after pamidronate treatment. Ambulatory subjects excreted significantly less N-telopeptide than motor-complete subjects at all time points. CONCLUSION: Intravenous pamidronate treatment and ambulatory ability in the first 6 months after an acute spinal cord injury prevents bone density loss.

Acute Disease↗

A digital subtraction radiography investigation of upper first molar proximal bone density changes in adolescents.

The aim of this in vivo study was to investigate the ability of digital subtraction radiography to monitor changes in proximal bone density, adjacent to the upper first molars, in a group of adolescents using the Digora direct digital radiographic system to acquire images. For 57 adolescents, assessments of changes in probing attachment level at the mesio- and disto-buccal surfaces of both upper first molars and proximal crestal bone density using digital subtraction radiography were made. At the conclusion of this 21-month study attachment loss was identified in 34 (17%) of the 204 sites analysed. For sites with attachment loss a mean decrease in bone density equivalent to 5.51 mm3 aluminium (Al) was found compared to 2.96 mm3 Al for those without (p < 0.001). For the 17 subjects with attachment loss a mean equivalent to 4.66 mm3 Al was lost from the crestal bone compared with 2.56 mm3 Al for the 40 subjects without attachment loss (p < 0.01). The correlation between attachment loss and bone density changes was poor for both sites (r = 0.13), p = 0.067) and mean scores for subjects (r = 0.24, p = 0.069). A visual qualitative assessment of bone density change found that 70.6% of sites with attachment loss compared to 62.4% of those without had a decrease in crestal bone density. This study suggests that it is possible to monitor bone density changes in adolescents, with a developing dentition, using digital subtraction radiography. Further, it is suggested that conventional probing assessments of attachment level may underestimate the level of destructive periodontal disease in this age group.

Adolescent↗

Determinants of bone density and prevalence of osteopenia among female runners in their second to seventh decades of age.

This is a cross-sectional study of spine and hip bone density (BMD) in 124 female athletes, aged 16-68 years, who trained for at least 3 hs/week. The aim was to document the effects of competitive running on BMD in women over a broad age range. Thirty-three subjects, aged <35 years, were currently oligo- or amenorrheic and, of the 50 who were >40 years, and who were now menstruating normally, 13 had previously been oligo- or amenorrheic. Fifty-two women <50 years of age had never had disturbed menses. Twenty-four older women were postmenopausal. Women who had never had menstrual disturbance had significantly increased bone density at the lumbar spine, femoral neck, and femoral trochanter, as compared with young normal European reference data (range from +0.4 population SD or T-score units to +1. 2 units according to measurement site and age group). In contrast, young amenorrheic or oligomenorrheic runners had reduced bone density, particularly at the spine (mean T score < -1.1), whereas older runners who previously had disturbed menses, but were now menstruating normally, had bone densities that were similar to sedentary young controls. Postmenopausal runners had bone density values that differed little from sedentary postmenopausal controls matched for time since menopause, after adjusting for the runners' lower body weight. Bone density outcomes were related to candidate explanatory variables. After taking into account the other variables, age, per se, influenced only the femoral neck and Ward's area. Years since last exposure to estrogen (at premenopausal levels) was an important determinant of bone loss at both hip and spine. Body weight had a beneficial influence on the femoral neck region, whereas (in contrast) height had a positive influence on the lumbar spine. Months of breastfeeding (totaled for all children) had a modest, positive influence, which was larger in the femoral measurement sites. There was no evidence of an effect of calcium intake or percent body fat on BMD at any site independent of these other effects. It is concluded that, with the consistent presence of normal premenopausal estrogen levels, running at least 3 hs/week substantially improves bone density, particularly at the proximal femur. This beneficial effect is reversed in the absence of the consistent past and current presence of normal menstrual function. There was no clear benefit of running seen on BMD in postmenopausal women, but premenopausal veteran athletes who started running after the age of 30 years were not disadvantaged compared with early starters.

Adolescent↗

[Menopausal bone density in healthy females of Voralberg. Lack of relation to anamnesis].

Bone density was evaluated in 182 healthy climacteric women. Women were recruted from a general prevention program. The results show deviation from 58.2 to 218.6--mean value 128.28, SD 30.91 mg/ccm K2HPO4. 28% of bone density values are under the fracture risk level citated in literature. No statistical relationship was found between bone density and anamnestic data--only the age at hysterectomy shows statistical correlation. The follow up after one year shows no predictive value of anamnestic data to the lost of bone mineral density.

Austria↗

Vitamin D receptor genotypes are related to bone size and bone density in men.

Three restriction fragment length polymorphisms in the vitamin D receptor gene have been associated with a low bone density in twin and female population studies, but no studies have been conducted exclusively in men. We studied 146 normal men aged 20-83 years. Bone density was measured in the spine, hip, whole body and forearm, and the Bsm polymorphism for the vitamin D receptor was detected by the polymerase chain reaction. Men with genotype BB tended to have a lower bone density at all but one site than the other genotypes. In the men < or = 50 years of age bone density in the forearm was 7% lower in the BB than the Bb and bb groups (P = 0.030) but bone mineral content did not differ between the groups. Bone area was greater in the BB genotype at all sites. This was statistically significant in the forearm (P = 0.026). We conclude that BB genotype is associated with lower bone density in men, which may be due to larger bone size rather than reduced bone mass.

Absorptiometry, Photon↗

Opposing changes in osteocalcin levels in bone vs serum during the acquisition of peak bone density in C3H/HeJ and C57BL/6J mice.

Our knowledge of the developmental changes in the concentration of serum and bone osteocalcin (OC) is limited. To investigate the interrelationship between skeletal and circulatory OC during acquisition of peak bone density in mice, we examined the temporal changes in the concentration of serum and bone OC from 3 to 12 weeks of age between C3H/HeJ (C3H) and C57BL/6J (B6), two commonly used inbred strains of mice with a large difference in bone density. We have demonstrated an increase in bone and decrease in serum OC during the acquisition of peak bone density in C3H and B6 mice which parallels an increase in bone mineral density. These two strains exhibited differential changes in the concentration of OC. C3H mice retained more OC in bone and secreted less into serum compared with B6, which coincides with the large differences in bone density between these two strains. These opposite changes of OC levels in bone and serum between C3H and B6 stress the importance of defining the genetic mechanisms underlying the differences in OC metabolism, differences that could be relevant to the acquisition and maintenance of bone mass in mice.

Aging↗

Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone density parameters in community-dwelling adolescent girls.

OBJECTIVE: Anorexia nervosa (AN) is an eating disorder that leads to a number of medical sequelae in adult women and has a mortality rate of 5.6% per decade; known complications include effects on hematologic, biochemical, bone density, and body composition parameters. Few data regarding medical and developmental consequences of AN are available for adolescents, in particular for an outpatient community-dwelling population of girls who have this disorder. The prevalence of AN is increasing in adolescents, and it is the third most common chronic disease in adolescent girls. Therefore, it is important to determine the medical effects of this disorder in this young population. METHODS: We examined clinical characteristics and performed hematologic, biochemical, hormonal, and bone density evaluations in 60 adolescent girls with AN (mean age: 15.8 +/- 1.6 years) and 58 healthy adolescent girls (mean age: 15.2 +/- 1.8 years) of comparable maturity. Nutritional and pubertal status; vital signs; a complete blood count; potassium levels; hormonal profiles; bone density at the lumbar and lateral spine; total body, hip, and femoral neck (by dual-energy x-ray absorptiometry) and body composition (by dual-energy x-ray absorptiometry) were determined. RESULTS: All measures of nutritional status such as weight, percentage of ideal body weight, body mass index, lean body mass, fat mass, and percentage of fat mass were significantly lower in girls with AN than in control subjects. Girls with AN had significantly lower heart rates, lower systolic blood pressure, and lower body temperature compared with control subjects. Total red cell and white cell counts were lower in AN than in control subjects. Among girls with AN, 22% were anemic and 22% were leukopenic. None were hypokalemic. Mean age at menarche did not differ between the groups. However, the proportion of girls who had AN and were premenarchal was significantly higher compared with healthy control subjects who were premenarchal, despite comparable maturity as determined by bone age. Ninety-four percent of premenarchal girls with AN versus 28% of premenarchal control subjects were above the mean age at menarche for white girls, and 35% of premenarchal AN girls versus 0% of healthy adolescents were delayed >2 SD above the mean. The ratio of bone age to chronological age, a measure of delayed maturity, was significantly lower in girls with AN versus control subjects and correlated positively with duration of illness and markers of nutritional status. Serum estradiol values were lower in girls with AN than in control subjects, and luteinizing hormone values trended lower in AN. Levels of insulin-like growth factor-I were also significantly lower in girls with AN. Estradiol values correlated positively with insulin-like growth factor-I, a measure of nutritional status essential for growth (r = 0.28). All measures of bone mineral density (z scores) were lower in girls with AN than in control subjects, with lean body mass, body mass index, and age at menarche emerging as the most important predictors of bone density. Bone density z scores of <-1 at any one site were noted in 41% of girls with AN, and an additional 11% had bone density z scores of <-2. CONCLUSIONS: A high prevalence of hemodynamic, hematologic, endocrine, and bone density abnormalities are reported in this large group of community-dwelling adolescent girls with AN. Although a number of these consequences of AN are known to occur in hospitalized adolescents, the occurrence of these findings, including significant bradycardia, low blood pressure, and pubertal delay, in girls who are treated for AN on an outpatient basis is of concern and suggests the need for vigilant clinical monitoring, including that of endocrine and bone density parameters.

Adolescent↗

[Effect of GnRH analogues on bone density in the vertebral column and the femur].

The objective of this study was to evaluate the effect on vertebral and femural bone density of the gonadotropin-releasing hormone (GnRH) analog administration. The changes in mineral bone density after 6 months discontinuation of the GnRH analog treatment were also measured. Forty-three premenopausal women with regular cycles and suffering from uterine myomatosis have been selected for the study. Twenty-eight women (group A) were treated with Goserelin 3.2 mg given as a depot every 28 days for 6 months. Fifteen women were treated with 10 mg of medroxyprogesterone acetate (MPA) from day 16 to day 25 of each month for 6 months. Vertebral and femural bone density was measured (by Hologic QDR-X 1000) just before the start of the study, at 6 months of treatment and at 12 months (after 6 months of discontinuation treatment). Significant loss of vertebral bone density was demonstrated in women treated with GnRH analog. After six months of treatment discontinuation bone mineral density did not recover the pretreatment values. Bone femural density showed a not significant decrease in the GnRH analog group. In our experience, the treatment with GnRH analog in premenopausal women induces a reduction in lumbar bone density that is not reversible after the treatment withdrawal; for this reason it would be safe to add at the GnRH analog a therapy which can prevent the bone loss.

Adult↗