Spine and femur BMD by DXA in patients with varying severity spinal osteoporosis

Summary Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1:-3SD deformations only; group 2: one-4SD deformation; group 3: two-four-4SD deformations; and group 4: 5 or more-4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20–40 years) and 109 postmenopausal normal women (average age 64, range 60–70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm² (P<0.01) and Ward's triangle 0.059 g/cm² (P<0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this crosssectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures.     

Low Bone Mass Density at Multiple Skeletal Sites, Including the Appendicular Skeleton in Amenorrheic Runners

The aim of this study was to investigate any difference in bone mass at different sites between female long-distance runners with amenorrhea and those with eumenorrhea. We compared 10 amenorrheic and 10 eumenorrheic athletes to determine whether athletes with amenorrhea have lower BMD in multiple skeletal regions, including weight-bearing lower limbs. The amenorrheic group had experienced menstrual dysfunction ranging from 3 to 43 months. As a further control group, 16 eumenorrheic soccer players were compared with the former two running groups regarding their BMD measurements. The two groups were matched for age, height, and amount of training. Areal bone mineral density (BMD) was measured and was found to be significantly lower in the total body, humerus, spine, lumbar spine, pelvis, femoral neck, trochanter, total femur, femur diaphysis, tibia diaphysis and in the nonweight-bearing head of the femur in the amenorrheic group. Body weight, BMI, fat mass, and body fat percent were significantly lower in the amenorrheic group. The differences in the BMD of the head, humerus, femoral neck, total femur, femur diaphysis, and tibia diaphysis disappeared when adjusted for body weight. Compared with the soccer group, the amenorrheic subjects had significantly lower BMD values at all sites except for the head, Ward's triangle, and femur diaphysis. Blood samples were obtained in the two running groups for analysis of osteocalcin, carboxy terminal telopeptide (ICTP), procollagen I (PICP), and estradiol. There were no significant differences between the groups but there was a strong tendency towards a lower estradiol level and a higher osteocalcin level in the amenorrheic group. A free estradiol index (FE₂) was derived as the ratio of estradiol to sex hormone binding globulin (SHBG) and was significantly lower in the amenorrheic group. No difference in their daily intake of total energy, protein, carbohydrates, fiber, calcium, and vitamin D was observed. However, both groups showed a surprisingly low energy intake in relation to their training regimens. Stepwise regression analyses revealed that weight was the best predictor of spine BMD in both groups. Estradiol and FE₂ were significant predictors of the BMD of the proximal femur in the eumenorrheic group, but did not predict any BMD site in the amenorrheic group. In conclusion, amenorrhea in athletic women affects trabecular and cortical bone in both axial and appendicular skeleton. However, some of the discrepancy can be explained by a lower body weight. Physical weight-bearing activity does not seem to completely compensate for the side effects of reduced estrogen levels even in weight-bearing bones in the lower extremity and spine. Received: 15 November 1997 / Accepted: 9 July 1998     

Bone mineral density measured by dual-energy X-ray absorptiometry in healthy finnish women

Summary A cross-sectional study of 351 healthy Finnish women aged 20–76 years was done to establish reference values of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DEXA). The effects of age and of several physical and lifestyle factors on BMD of the lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle area) were investigated. Altogether 58 women were excluded from the final analysis due to significant spinal osteoarthritis or other diseases or drugs known to influence calcium or bone metabolism. The precision of the method was 0.9, 1.2, 2.7, and 2.4% in the lumbar, femoral neck, Ward's triangle and trochanter area, respectively. Lumbar BMD was increased by 30% (P<0.001) in 15 patients with osteoarthritis (21% of women 50 years or older), but it was apparently unaffected in 5 cases with aortic calcification. Except for the trochanter area, BMD diminished along with age, and this was significant after the menopause. The peak of mean BMD was observed at the age of 31–35 years in the spine and at the age of 20–25 years in the femoral neck and Ward's triangle. BMD was in a positive relationship to weight both in premenopausal and postmenopausal women and to the use of oral contraceptives in premenopausal women and to that of estrogen replacement therapy in postmenopausal women. Labors and pregnancies had a weak positive effect on BMD in premenopausal women. As compared with nonusers premenopausal women who had used alcohol showed a slightly decreased BMD of Ward's triangle. In postmenopausal women there was a positive correlation between alcohol intake and BMD.     

Bone mineral density of the proximal femur and lumbar spine in glucocorticoid-treated asthmatic patients

The importance of the proximal femur as a site of osteoporotic fractures, the development of techniques for bone mineral density (BMD) measurement at this site and the apparent selectivity of the osteopenic effects of glucorticoids have focused attention on the assessment of proximal femoral BMD in steroid-treated subjects. We have, therefore, measured BMD (Lunar DPX) in the lumbar spine and proximal femur of 31 asthmatic patients receiving long-term glucocorticoid therapy (mean ± SEM dose 16 ± 1 mg prednisone/day, mean duration 10 ± 2 years). BMD values expressed as the percentage of normal age- and sex-appropriate mean values, after weight adjustment, were as follows: lumbar spine 80 ± 2%, femoral neck 83 ± 2%, Ward's triangle 78 ± 3% and trochanter 86 ± 2%. All these values were significantly less than control (p<0.0001) and the decrement in BMD was more marked in Ward's triangle than at the other two femoral sites (p<0.05). In all regions BMD was unrelated to dose or duration of steroid treatment. It is concluded that there are reductions in the BMD of the lumbar spine and proximal femur in glucocorticoid-treated asthmatics, probably reflecting the mixed cortical/trabecular makeup of both regions.     

Total and regional bone mass in female soccer players

This cross-sectional study investigated bone mass in female athletes participating in an impact-loading sport (soccer), and evaluated whether any changes in bone mass could be related to the type of weight-bearing loading and muscle strength. The group of soccer players consisted of 16 second-division female players (age 20.9±2.2 years) training for about 6 hours/week. The reference group consisted of 13 nonactive females (age 25.0±2.4 years) not participating in any kind of regular or organized sport activity. The groups were matched according to weight and height. Areal bone mineral density (BMD) was measured in total body, head, lumbar spine, femoral neck, Ward's triangle, trochanter, the whole femur and humerus, and in specific sites in femur diaphysis, distal femur, proximal tibia, and tibia diaphysis using dual X-ray absorptiometry. Isokinetic concentric peak torque of the quadriceps and hamstring muscles was measured using an isokinetic dynamometer. The soccer players had significantly (P<0.05-0.01) higher BMD in the lumbar spine (10.7%), femoral neck (13.7%), Ward's triangle (19.6%), nondominant femur and humerus (8.2 and 8.0%, respectively), distal femur (12.6%), and proximal tibia (12.0%) compared with the nonactive women. There was no significant difference in muscle strength of the thigh between the two groups. In the nonactive group, muscle strength in the quadriceps and especially hamstrings, was correlated to BMD of the adjacent bones (whole femur, hip sites) and also to distant sites (humerus). In the soccer group, there were no correlations between muscle strength and BMD of the adjacent and distant bones. Soccer playing and training appears to have a beneficial effect on bone mass in young females, and it seems that there is a site-specific skeletal response to the type of loading subjected to each BMD site. Muscle strength in the thigh is not related to bone mass in female soccer players.     

Changes in bone density in women starting hormone replacement therapy compared with those in women already established on hormone replacement therapy

It is well established that hormone replacement therapy (HRT) will prevent postmenopausal loss of bone. However, it is not known to what extent HRT will continue to affect bone mineral density (BMD) in women established on HRT compared with those commencing treatment. We recruited 48 healthy early postmenopausal women into a prospective, comparative study. Twenty-nine women had never taken HRT (group A) whilst 19 women were already taking HRT (group B) (conjugated equine oestrogens, 0.625 mg daily; mean (±SD) years of use 2.2 (1.5) years). All of the women were started on, or switched to, micronized 17-oestradiol (2 mg/day) continuously with dydroges-terone (10 mg/day) for the first 14 days of each cycle. BMD measurements were performed at the lumbar spine and proximal femur using dual-energy X-ray absorptiometry (DXA) at baseline and after 12 and 24 months of treatment. Group A showed a significantly greater increase in lumbar spine BMD after 12 months (mean (±SD)=5.3 (4.6)%) compared with group B (mean(±SD)=2.1 (2.1)%) and 24 months of treatment (group A, mean(±SD)=6.4 (5.2)%; group B, mean (±SD)=2.3 (2.6)%; bothp<0.01). Femoral neck and Ward's triangle BMD increased significantly in both groups but there were no significant differences between the groups. Baseline BMD correlated with change in lumbar spine BMD for women in group A after 12 months (r=–0.67,p<0.01) and 24 months of treatment (r=–0.59,p<0.05). These data demonstrate that HRT has the greatest effect on BMD when it is first administered, especially in those women with low BMD, but improvements may still be observed in women continuing HRT in the longer term.     

A Prospective Study of Bone Loss in Menopausal Australian-Born Women

Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46–59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14–41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n= 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of 70.9% (0.4%) at the lumbar spine and 70.7% (0.6%) at the femoral neck (both p50.05 compared with women who remained premenopausal). In the women who became postmenopausal (n= 42) the mean annual changes in BMD were 72.5% (0.2%) at the lumbar spine and 71.7% (0.2%) at the femoral neck (both p50.0005), and in the women who remained postmenopausal (n= 60) they were 70.7% (0.2%) per year and 70.5% (0.3%) per year respectively (both p50.05), compared with women who remained premenopausal. In the 1–3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p50.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n= 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p50.005). In the women who remained postmenopausal there was an association between baseline body mass index (BMI) and percentage change per year in femoral neck BMD (p50.05), such that women with higher BMI had less bone loss. In conclusion, during the time of transition from peri- to post-menopause, women had accelerated BMD loss at both the hip and spine. Received: 23 June 1997 / Accepted: 5 November 1997     

Role of oral pamidronate in preventing bone loss in postmenopausal women

We have performed a 2-year prospective double-masked study to determine whether the bisphosphonate pamidronate can prevent bone loss in postmenopausal women and its optimal dosage regimen. One hundred and twenty-one such women (mean ± SD age 57.6±3.4 years; mean ± SD time since menopause 7.5±3.5 years) were randomized to receive either oral pamidronate (300 mg/day) for 4 weeks every 4 months (group A), oral pamidronate (150 mg/day) for 4 weeks every 2 months (group B) or identical placebo capsules (group C). Bone mineral density (BMD) measurements at the lumbar spine and proximal femur were performed at baseline and at 6-month intervals for 2 years using dual-energy X-ray absorptiometry. BMD at the lumbar spine (L2–4) increased significantly in groups A and B after 2 years of treatment (mean ± SD 2.8±2.1% and 3.0±2.9% respectively, bothp<0.001) but decreased in the placebo group (–1.6±3.1%,p<0.01). Identical results were seen for BMD at the femoral neck, which increased significantly in groups A and B after 2 years of treatment (1.2±2.3% and 1.3±2.9% respectively, bothp<0.05) but decreased in the placebo group (–1.9±3.9%,p<0.05). There were significant differences over 2 years between the groups at all anatomical sites (lumbar spine, femoral neck and trochanteric region, allp<0.001; Ward's triangle,p<0.01). However, there were no significant differences between groups A and B, suggesting that the two treatment regimens were equally effective in conserving BMD. There were, however, marked differences in tolerability between the two treatment regimens: 13 women (34%) in group A withdrew from the study because of side-effects, but only 5 women (12%) in group B, which was comparable with placebo. These data demonstrate that intermittent oral pamidronate will prevent bone loss from the lumbar spine and proximal femur of postmenopausal women, and that the more frequent but lower dose regimen is well tolerated.     

The relationship between endogenous estrogen,sex hormone-binding globulin,and bone loss in female residents of a rural Japanese community: the Taiji Study

 The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants—50 women in each of four age decades—were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal (n= 38), perimenopausal (n= 14), postmenopausal group 1 (5 years or less since menopause; n= 18), and postmenopausal group 2 (6 years or more since menopause; n= 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up (P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle BMD at follow-up (P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck (P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Ward's triangle (P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter (P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone. Received: November 29, 2001 / Accepted: February 28, 2002     

Role of persistent amenorrhea in bone mineral metabolism of young hemodialyzed women

BACKGROUND: Chronic renal failure in women is frequently associated with endocrine disturbances leading to menstrual disorders. However, most studies on renal osteodystrophy have not taken into account the possible role of these hormonal disturbances on the pathogenesis of bone alterations seen in these patients. In the present study, we evaluated bone mineral metabolism in a group of young hemodialyzed women with persistent amenorrhea and compared them with similar women with regular menstruation. METHODS: We studied 74 women who were further subdivided into 43 women with regular menstrual periods and 31 women with persistent amenorrhea, defined as the absence of menstrual bleeding for more than six months. In all patients, we performed a bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, intact parathyroid hormone (iPTH), sexual hormone determinations that included total estradiol, follicle-stimulating (FSH), and luteinizing hormone and markers of bone resorption such as the procollagen type 1 cross-linked carboxy-terminal telopeptide (ICTP). RESULTS: Serum calcium, phosphorus, and iPTH were similar in both groups. Serum alkaline phosphatase was higher in amenorrheic women. Although the total serum estradiol concentration was normal in the amenorrheic women when compared with nonuremic women, the values were significantly lower than those in regularly menstruating women. Serum FSH and ICTP values were significantly higher in the amenorrheic women. Trabecular BMD in the lumbar spine was also significantly lower in the amenorrheic women compared with regularly menstruating dialysis patients. Lumbar spine BMD and total estradiol levels correlated significantly in the amenorrheic group. CONCLUSIONS: These studies show that persistent amenorrheic young women on dialysis have lower trabecular BMD and evidence of increased bone resorption when compared with normal menstruating women on dialysis. The possible impact of these results in the natural history of the uremic osteodystrophy remains to be determined.     

Differential action of pamidronate on trabecular and cortical bone in women with involutional osteoporosis

Since osteoporotic fractures are mainly related to the diminution of the bone mineral density (BMD), the effect of pamidronate (3-amino-1-hydroxy-propylidene) 1,1-bisphosphonate on the BMD of the spine, proximal femur and radius shaft was evaluated in an initial cohort of 35 postmenopausal women with at least one vertebral fracture due to involutional osteoporosis.Pamidronate was given continuously during 18 months in a daily oral dose of 4.8 to 6.0 mg/kg supplemented with calcium (1 g/day).BMD — measured by dual photon absorptiometry — increased after one year 5.3±1.0% (P<0.001) in lumbar spine and 5.3±1.5% (P<0.001) over trochanter. However no significant changes were observed in the BMD of the femoral neck, Ward's triangle or in the cortical bone of the radius shaft measured by single photon absorptiometry.Pamidronate also decreased significantly urinary hydroxyproline-creatinine excretion after 6 months and thereafter maintained a plateau. After 18 months of treatment the diminution was 42.6±4.9% (P<0.001).The differing effects of pamidronate on the BMD of lumbar spine and proximal femur might be ascribed to dissimilarities between the proportions of trabecular and cortical bone in these. These results suggest that pamidronate may be prescribed to prevent fractures in cases of involutional osteoporosis with a significant decrease of BMD in lumbar spine and/or trochanter.     

Dual-energy X-ray absorptiometry in normal women: A cross-sectional study of 717 finnish volunteers

The bone mineral density (BMD) of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry in 717 healthy women aged 20–70 years. The maximal mean BMD was found at the age of 35–39 years in the spine and at the age of 20–24 in the femoral neck and Ward's triangle. No significant change in lumbar BMD was found from the age of 20 to 39 years. The spinal BMD values were relatively stable from age 20 to 39 years, whereas a linear decrease in BMD in the femoral neck and Ward's triangle was already apparent in the youngest age group (20–24 years). The major fall in BMD in all sites was related to the menopause. The overall decreases in BMD from the peak values to those at age 65–70 years were 20.4%, 19.0% and 32.6% in the lumbar spine, femoral neck and Ward's triangle, respectively. The correlation of trochanteric BMD with age was poor. BMD was positively correlated with weight in all measurement sites. Nulliparity was found to be a risk factor for osteoporosis. The present study confirmed that the menopause has a significant effect not only on spinal BMD but also on femoral BMD. Lumbar BMD was lower and BMDs in the proximal femur were higher in Finnish women than in white American women. This emphasizes the importance of national reference values for BMD measurements.     

Risk for developing osteoporosis in untreated premature menopause

Summary The bone mineral density (BMD) of the lumbar spine and proximal femur was determined by dual photon absorptiometry in 32 women with untreated premature menopause (cessation of menses before 45 years of age). The BMD of the spine and proximal femur in four obese patients was not different from the BMD of the age-matched controls. On the contrary, the BMD of the nonobese females with premature menopause was significantly lower with respect to the average values found in healthy young women, in age-matched and menopause-matched controls. The BMD deficit was greater over the lumbar spine than in the proximal femur. Forty three percent of nonobese patients were already under the vertebral fracture threshold and 25% of nonobese patients were below the hip fracture threshold. The BMD deficit in the lumbar spine was correlated to the loss observed in the femoral neck (r=0.59, P<0.001), in the trochanter (r=0.65, P<0.001) and in the Ward's triangle (r=0.73, P<0.001). A negative correlation was observed between years of menopause and the BMD of the lumbar spine (r=-0.39, P<0.05). The results indicate the high individual risk for osteoporotic fractures in nonobese females with untreated premature menopause. The BMD loss was greater over the skeletal areas that are predominantly composed of trabecular bone compared with cortical bone.     

Bone mass after long-term euthyroidism in former hyperthyroid women treated with (131)I influence of menopausal status.

The objective of this study was to assess bone mineral density (BMD) and bone markers in former hyperthyroid females after long-term euthyroidism (>4 yr) following (131)I therapy, as well as the potential influence of the timing of menopause. Twenty-six females ages 57 +/- 8 yr previously diagnosed with hyperthyroidism and treated with (131)I who were euthyroid for a minimum of the last 4 yr (10 +/- 5 yr) were studied. Eighteen patients (69%) were on levothyroxine (LT(4)) replacement therapy for 9 +/- 4 yr. BMD (g/cm(2) and Z-score) was measured by dual X-ray absorptiometry in the lumbar spine, femoral neck, and Ward's triangle. BMD (Z-score) was lower than the normal reference values for the Spanish population in all sites (lumbar spine: -0.65 +/- 1.13; femoral neck: -0.47 +/- 0.95; Ward's triangle: -0.37 +/- 0.88). No differences were found between BMD values according to the etiology of the hyperthyroidism or current LT(4) therapy. Current postmenopausal patients (n = 21) showed lower BMD than current premenopausal patients in the lumbar spine and femoral neck (p < 0.05). Those women who were postmenopausal at the time of the (131)I therapy (n = 15) also had lower lumbar spine BMD than premenopausal patients (p = 0.01), while no significant difference in BMD was seen according to the menopausal status when hyperthyroidism was diagnosed. Former hyperthyroid patients after long-term euthyroidism following (131)I therapy showed reduced BMD at the lumbar spine and proximal femur. Menopausal women showed a greater reduction in bone density. The menopausal status at the time of diagnosis did not seem to have long-term effects in bone density; nevertheless, an early therapeutic intervention in premenopause is suggested to reduce bone loss.     

Bone density in white Brazilian women: Rapid loss at the time around the menopause

Dual energy x-ray absorptiometry (DXA) was used to measure bone mineral density (BMD) of the lumbar spine and proximal femur (neck, Ward's triangle, and trochanter) in 417 normal women (aged 20–79) living in São Paulo, Brazil. Bone density decreased with age at all sites. At the spine, the greatest decrease occurred during the sixth decade, with an average 11.4% bone loss compared with the previous decade. Stratifying the subjects according to menopausal status revealed that the fastest bone occurred at the time around the menopause (ages 45–60) when the rate of bone loss (-0.66%/year) was almost twice as rapid as in postmenopausal women (-0.39%/year). Although significant linear rates of bone loss were detected in all proximal femur sites before the menopause, a menopause-dependent pattern was less evident that at the spine. Lifetime rates of bone loss at the appendicular skeleton were-0.43,-0.62, and-0.35%/year at the femoral neck, Ward's triangle, and trochanteric area, respectively. After the menopause, BMD declined with menopausal age at all sites, although the rate of bone loss was faster at the femoral neck (-0.62%/year) and Ward's triangle (-0.84%/year) than at the spine-0.49%/year). The results are consistent with the notion that in women, the fastest bone loss occurs at the time round the menopause, most likely consequent to ovarian failure; and that faster rates of bone loss are detected at the proximal femur than at the lumbar spine in late postmenopausal women.     

Parity and bone mineral density in middle-aged women

A retrospective study was carried out to determine the relationship between parity and bone mineral density (BMD) in middle-aged women. Eight hundred and twenty-five woman aged 41–76 years were recruited from four general practice registers in Cambridge. Subjects were unselected as to their health status. Each subject completed a detailed health questionnaire. Participation rate was 50%. The main outcome measure was BMD measured at the spine (L2–4,n=825) and hip (neck, intertrochanter and Ward's triangle;n=817) by dual-energy X-ray absorptiometry (DXA) using the Hologic QDR-1000 densitometer. It was found that the unadjusted mean BMD was significantly higher at all sites among the parous women (p=0.031 to <0.00001), and remained significantly higher at the femoral neck (p=0.025), intertrochanter (p=0.001) and Ward's triangle (p=0.045) after adjusting for age and body mass index (BMI). Similar findings were seen after stratifying for potential confounding variables. There was a consistent upward trend of BMD with increasing parity at all sites. Parity remained a significant independent predictor of BMD at all sites after controlling for age, BMI, menopausal status, oral contraceptive and hormone replacement therapy use, smoking status and breast-feeding status in multiple linear regression analyses. There was, on average, a 1.0% increase in BMD per live birth. Our findings therefore suggest a positive relationship between parity and bone mass.     

The use of etidronate and calcium versus calcium alone in the treatment of postmenopausal osteopenia: Results of three years of treatment

The purpose of this open, prospective, controlled, randomized trial was to study the effect of intermittent, cyclic etidronate on the bone mass of osteoporotic postmenopausal women with or without fractures. Eligible subjects were asymptomatic women less than 75 years old who had been amenorrhoeic for at least 1 year. Those with secondary osteoporosis were excluded. Subjects also had to be ambulant with a bone mineral density (BMD) of the lumbar spine >1 SD below that of age matched controls (Z-score < –1 SD). Eighty patients were enrolled, of whom 65 were recruited through a screening programme conducted in the practices of two general practitioners. The remaining patients were from other referrals. The subjects were randomized to two groups of 40 women. Treatment regimens were as follows. The etidronate group was treated with etidronate 400 mg once daily for 14 days followed by 76 days of 500 mg of elementary calcium once daily; this cycle was repeated every 3 months. The calcium group took 500 mg of elementary calcium once daily. The groups were not different in age, height, weight, time since menopause, BMD at baseline and prevalent vertebral fractures. In 50 patients (28 in the etidronate group and 22 in the calcium group) no vertebral fractures were present (67%). Sixty-four patients (35 in the etidronate group and 29 in the calcium group) completed the 3 years of the study. In the etidronate group the mean BMD of the lumbar spine, femoral neck, trochanter and Ward's triangle increased by 5.7%, 1.4%, 7.1% and 10.9% from baseline values respectively (p<0.05 at all sites except for the femoral neck). In the calcium group no significant changes from baseline were found at any time point at any site after 3 years, except for the femoral neck, where BMD at 156 weeks decreased significantly by 3% (p<0.003). In 3 patients, all in the calcium group, six new fractures were found. There were no serious adverse effects. We conclude that intermittent, cyclic treatment with etidronate causes a significant increase in the BMD of the lumbar spine and the proximal femur in osteopenic postmenopausal women, and that treatment is safe and has no serious adverse effects.     

Sequential Therapy With Recombinant Human IGF-1 Followed by Risedronate Increases Spine Bone Mineral Density in Women With Anorexia Nervosa: A Randomized,Placebo-Controlled Trial

Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF-1 followed by 6 months of risedronate (“rhIGF-1/Risedronate”) (n = 33), 12 months of risedronate (“Risedronate”) (n = 33), or double placebo (“Placebo”) (n = 16). Outcome measures were lumbar spine (1° endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/Risedronate (p = 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1/Risedronate than the Risedronate or Placebo groups (p < 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1/Risedronate than Placebo group (p < 0.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF-1 was well tolerated. Therefore, sequential therapy with rhIGF-1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Treatment of Reduced Bone Mineral Density in Athletic Amenorrhea: A Pilot Study

There is considerable concern about the adverse effects on the skeleton of loss of menstrual function as a result of athletic activity, as well as uncertainty as to how it should be managed clinically. In a pilot intervention study 34 elite middle and long-distance runners, aged 18–35 years, with menstrual irregularity due to their athletic activity were randomized to three groups: (A) to receive hormone replacement therapy (HRT) and 1000 mg calcium per day (n= 10), (B) to receive 1000 mg calcium per day (n = 14), (C) a control group who received no treatment (n= 10). Bone mineral density (BMD) was measured in the left hip and lumbar spine (L2–4) using dual-energy X-ray absorptiometry. Results were first analyzed according to whether menstruation returned, either naturally or secondary to HRT (EU), and compared with those from subjects who remained amenorrheic (AM). During the first year BMD increased in the EU group in Ward’s triangle (3.8%) and the lumbar spine (4.1%; both P<0.05). BMD fell in the AM group in all regions and the between-group differences were 5.6% (p<0.02) in Ward’s triangle, 5.8% (p<0.02) in L2–4 and 3.9% in the trochanter (p<0.05). An ‘intention to treat’ analysis was then performed. It was found that the mean relative improvement at 1 year in spinal BMD was only 1.5%, due to return of menses in some of the controls and withdrawals from treatment in the treatment group. In consequence, a trial designed to show, with 80% power and 5% significance, a measurable benefit in lumbar spine BMD resulting from allocation to HRT treatment would require about 1150 athletes with amenorrhea or oligomenorrhea. These numbers could be reduced substantially to 380 subjects by confining the trial to completely amenorrheic athletes, who in this study were less likely to regain menses. For these and other logistical reasons, an HRT trial in amenorrheic athletes could only be successfully organized through international collaboration. This study illustrates the major effects of treatment withdrawals and instability of menstrual status on the design of longitudinal studies on the bony effects of menstrual dysfunction prior to menopause. Received: 5 August 1998 / Accepted: 11 March 1999     

A longitudinal study of supine lateral DXA of the lumbar spine: A comparison with posteroanterior spine,hip and total-body DXA

We report a study to assess whether supine lateral dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine provide better data for monitoring response to treatment than alternative measurement sites such as the posteroanterior (PA) spine, hip and total body. The study population was 152 women enrolled in a placebo-controlled clinical trial of cyclical etidronate therapy. All subjects were 1–10 years after the menopause with bone mineral density (BMD) between 0 and –2 SD of age-matched normal women. Paired PA and lateral spine, left hip and total-body DXA scans were performed at baseline, 1 year and 2 years on a Hologic QDR-2000. One hundred and thirty-one subjects completed the study. Mean percentage change from baseline at 2 years in the treated (n=61) and control (n=70) groups was calculated for vertebral body, width-adjusted (WA) vertebral body, mid-vertebral body and WA mid-vertebral body BMD measurements on the lateral scans and compared with the percentage changes in PA spine, femoral neck, trochanter, Ward's triangle and total-body BMD. The long-term precision for each BMD measurement site was obtained by linear regression analysis in subjects taking placebo. Overall treatment effect, defined as the difference in the percentage change in BMD in the two treatment groups at 2 years, was divided by long-term precision to give an index of the ability of each site to monitor response to treatment. Results (and standard errors) normalized to the ratio of treatment effect/precision for PA spine BMD were as follows: PA spine, 1.00; vertebral body, 0.89 (0.14); WA vertebral body, 0.78 (0.14); mid-vertebral body, 0.65 (0.14); WA mid-vertebral body, 0.60 (0.13); femoral neck, 0.35 (0.15); trochanter, 0.45 (0.15); Ward's triangle, 0.59 (0.22); total body, 0.52 (0.19). Although treatment effect was larger for lateral than for PA spine BMD, this advantage was offset by the greater precision errors. PA spine BMD remains the optimum measurement for longitudinal studies in recently postmenopausal women.