Anders Gotfredsen

Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause

The reduction in cardiovascular risk induced by hormone replacement therapy is only partly explained by changes in serum lipids and lipoproteins. As body composition and body fat distribution in particular are independent predictors of cardiovascular disease, we investigated the effect of postmenopausal hormone therapy on body composition parameters directly measured. Sixty-two early postmenopausal women were followed up for 2 years in a prospective, randomized, placebo-controlled study. We found that combined estrogen-progestogen therapy prevented the increase in abdominal fat after menopause (P less than .05), and that this effect was independent of the effect on serum lipids and lipoproteins. The therapy reduced postmenopausal bone loss significantly (P less than .001), whereas it did not have a statistically significant influence on total body fat mass or total lean body mass. The findings of the present study suggest that some of the protective impact of postmenopausal hormone therapy on cardiovascular disease may be explained by the effect on body composition, in particular abdominal fat.

Measurement of lean body mass and total body fat using dual photon absorptiometry

We describe a method for measuring the lean body mass (LBM) and total body fat (FAT) by dual photon absorptiometry (DPA). A total body rectilinear scan was employed with a radiation source of 1 Ci 153Gd. The reliability of estimating the lean percent was assessed in vitro using limb phantoms consisting of ox muscle, lard, and human bone. The precision and accuracy in vitro of the lean percent determination were 1.5% and 1.9%, respectively. The accuracy error in vivo of measuring the total mass of soft tissues (TMST) was approximately 1.4%, thus yielding an overall accuracy error of the LBM of about 2.5%. The precision in vivo of the lean percent and the LBM in kg of duplicate measurements on five healthy subjects was 2.5% and 2.2%, respectively. Other estimates of the LBM and FAT, ie, the calculation according to Boddy et al6 and the skinfold thickness measurement (triceps and subscapular), were compared to the DPA measurement in 100 healthy subjects. High correlations were found between the FAT or FAT% by DPA versus (1) the FAT or FAT% calculated according to the formulae of Boddy et al, and (2) the skinfold thickness. The correlations between the FAT and FAT% by Boddy et al and the skinfold thickness were, however, moderate. The correlation between LBM by DPA and LBM by Boddy et al was highly significant (r = 0.96, SEE = 4.4%). We conclude that LBM and FAT measurements using DPA have precision and accuracy errors that are commensurate with a reliable estimation of the gross body composition.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of tamoxifen on bone mineral content in premenopausal women with breast cancer

Thirty‐one of 62 consecutive premenopausal women with primary cancer of the breast completed a 1‐year investigation period, receiving either 30 mg tamoxifen daily (15 patients) or placebo (16 patients). They were examined at the operation (t0) and at 3‐month intervals (t1, t2, t3, and t4). Bone mineral content (BMC) was measured at operation and after 12 months. Fifty‐six patients with benign tumors were included as healthy controls. All values of both cancer treatment groups and of the benign tumor group were comparable at the time of operation. BMC decreased significantly in both cancer patient groups when 12‐month values were compared to the initial level (tamoxifen, −3.2%, P < 0.001 and placebo −2.5%, P < 0.01). However, no significant difference in BMC changes was noted between tamoxifen and placebo treatment. The serum phosphate was significantly decreased in the tamoxifen treatment group at each examination. In the placebo group, the alkaline phosphatase level increased significantly at each examination, whereas the serum magnesium fell at the 6‐ and 12‐month examinations. All other biochemical indices of calcium metabolism were basically unchanged. It is concluded that BMC is reduced in metastatic breast cancer through osteolytic metastatic bone foci. Tamoxifen also decreases the BMC. It is, however, unclear if this effect is due to a progression of the disease in spite of the treatment or if it is caused by a direct action of tamoxifen on bone.

Lean body mass in small for gestational age and appropriate for gestational age infants

Dual photon absorptiometry using 153Gd in a whole-body scanner was used to measure lean body mass (LBM) in 51 newborn infants. LBM% decreased exponentially with increasing gestational age in both small for gestational age (SGA) and appropriate for gestational age (AGA) infants. In preterm SGA and AGA infants LBM was 104% and 103%, respectively, indicating that no fat was detectable. In term SGA infants LBM was 98%, which corresponded to 48 gm fat on average, and in term AGA infants LBM was 87%, which corresponded to 452 gm fat on average. The LBM%, ponderal index, and skinfold thickness were significantly different between AGA and SGA infants. Infants with clinical signs of intrauterine wastage had significantly higher LBM% than did infants without signs of weight loss. Our results on LBM% by dual photon absorptiometry agree with earlier dissection data; the clinically applicable methods of (1) height combined with weight (i.e., ponderal index), (2) skinfold thickness, and (3) scoring by clinical observations are useful for the estimation of lack of fat as an indicator of intrauterine growth retardation.

Is postmenopausal bone loss an age-related phenomenon?

SummaryForearm bone mineral content (BMC), an index of skeletal mineralization, and lean body mass (LBM), an index of the muscle mass in the body, were calculated in 574 healthy, white subjects, aged 20–89 years. In women, there was no significant change in BMC with age until the menopause. Thereafter, a significant decline averaging 15% per decade was found up to the age of 70 years, after which it was 10% per decade. In men, there was a significant overall decline of about 4% per decade from the age of 20. When BMC was corrected for LBM, the age-related fall in men disappeared, while remaining without a significant trend in premenopausal women. This was, however, not the case in women after the menopause, where a significant decline of about 12% per decade was noted. These data clearly demonstrate that the major contribution to the well-known bone loss in postmenopausal women is not a simple age-related phenomenon. The development of osteoporosis must be due to some additional bone-diminishing effect on the female skeleton, most likely the absence of estrogen.

Bone composition in the distal forearm

Recent data have indicated that measurements of bone mass in the very distal part of the forearm is superior to more proximal measurements in identifying osteoporosis. Bone slices from the distal part of the forearm were obtained from 16 necropsies and the trabecular fraction of the total dry bone weight was measured in adjacent bone slices, 8 mm thick. Prior to autopsy bone mass at the corresponding sites was measured using a multipath single photon absorptiometric method by which scans are obtained proximal (proximal BMC) and distal (distal BMC) to the site, where the ulna and radius are 8 mm apart. The accuracy of bone measurements at the two sites was virtually similar (r = 0.98 and r = 0.94, respectively). In both areas the amount of trabecular bone increased towards the metaphysis with a trabecular/cortical ratio ranging from 10 to 60% (wt/wt). If bone composition is known it is possible to estimate rates of bone loss from the two compartments.

Bone mass, bone structure and vertebral fractures in osteoporotic patients

The clinical severity of bone disease was studied in 44 post-menopausal osteoporotic women. Spinal x-rays were assessed and compared to objective measurements of bone mass and bone structure; forearm bone mineral content (BMCarm) by single photon absorptiometry, total body bone mineral content (TBBM), and spinal bone mineral content (BMCspine) by dual photon absorptiometry, and corrected cortical width (C Cor W), trabecular bone volume (TBV), and indices of trabecular microstructure by iliac crest biopsy. For comparison data of BMCarm, TBBM and BMCspine in 25 post-menopausal normals are shown. The results showed a reduction in amount of both cortical and trabecular bone in the fracture patients compared to normals. A subdivision of the fracture patients into two groups constituting 26 patients with wedge fractures alone and 18 patients with compression (+wedge) fractures showed that the latter group had a further predominantly trabecular bone loss and a further deteriorated trabecular microstructure. On an individual basis no agreement between clinical severity of bone disease and amount and structure of bone could be demonstrated.

Does a single local absorptiometric bone measurement indicate the overall skeletal status? Implications for osteoporosis and osteoarthritis of the hip.

SummaryRegional bone mineral content (BMC) and density (BMD) (head, arms, chest, spine, pelvis, legs) of a total body dual photon153Gd absorptiometry (DPA) scan were measured in 20 healthy postmenopausal women, 27 postmenopausal women with hip fracture, and 17 postmenopausal women with osteoarthritis of the hip. In addition, local BMC and BMD were measured in the proximal and distal regions of the distal forearm (BMCprox, BMDprox, BMCdis, BMDdist) by single photon absorptiometry (SPA); and in the lumbar spine (BMCL2-L4 and BMDL2-L4) by153Gd DPA. The overall impression was a reduction of bone mass in hip fracture patients compared with healthy controls and an increase in the bone mass of osteoarthritic patients. These results were valid using both regional values of the total body scan, and local forearm and lumbar spine measurements, and statistically significant using one-way analysis of variance. There were, however, also significant within-group between-region differences (one-way analysis of variance), showing that the bone mass of the pelvis and legs in hip fracture patients was more reduced than in the remaining skeleton; in osteoarthritic patients it was not increased but rather unchanged or slightly reduced. The differences between the level of the three local measurements (BMDprox BMDdist BMDL2-L4), on the one hand, and the level of the six regional BMD values, on the other hand, were investigated by the two-way analysis of variance: local measurements = rows; regional values = columns. This analysis showed that none of the three local measurements was statistically better than the other two in predicting the overall level of skeletal bone mass as judged by the six regional values. We conclude that serious osteoporotic bone loss has a generalized nature, however, with a tendency towards lower values in the regions affected by fracture (viz: low bone mass in the legs of femoral neck fracture patients). Osteoarthritis may be associated with a high bone mass in most areas, but low values in the affected regions. Local lumbar spine measurement of bone mass by DPA is not superior to local forearm measurement of bone mass by SPA in predicting the nature of overall osteoporotic or osteoarthritic bone change.

THE DIAGNOSTIC VALIDITY OF LOCAL AND TOTAL BONE MINERAL MEASUREMENTS IN POSTMENOPAUSAL OSTEOPOROSIS AND OSTEOARTHRITIS

Assessment of different forms of prevention and treatment of bone mineral loss depends upon valid and precise methods to assess bone mass. We have here studied four groups of women: 45 healthy premenopausal women, 37 healthy postmenopausal women, 21 women with osteoarthritis and 20 with hip fractures. Bone mass was measured in the spine and total body by dual photon absorptiometry and in two forearm sites (proximal and distal bone mineral content (BMC) by single photon absorptiometry. The long‐term (1 year) reproducibility was 1.2% for proximal BMC, 1.6% for distal BMC, 5.5% for spinal BMC, and 21% for total body bone mass (TBBM). In the early postmenopausal years bone mass was mainly reduced in areas with a high content of trabecular bone. In elderly postmenopausal women and women with hip fractures bone mass was almost identical in all four sites studied. The osteoarthritic patients had an 18% reduction of bone mass in the forearms and in TBBM, whereas the spinal bone mass was only reduced by 6%. In all subgroups TBBM could be predicted from the forearm measurements with standard errors of estimates of 9–13%. When the osteoarthritic women were excluded spinal bone mass could be predicted from both forearm measurements with a standard error of 15% (r= 0.74). The distal forearm BMC seems to be a more accurate estimate of spinal bone mass than does the proximal measurement. Of the 20 patients with hip fracture 16 had a distal forearm value below the premenopausal normal range, whereas spinal bone mass was subnormal in only eight (P < 005). We conclude that bone loss is universal in patients with hip fracture and measurements of forearm bone mass will meet most clinical and research demands.

Different actions of vitamin D2 and D3 on bone metabolism in patients treated with phenobarbitone/phenytoin

SummaryIn 22 epileptic outpatients treated for at least 1 year with phenobarbitone/phenytoin the local and total bone mass, together with serum and urinary indices of calcium metabolism, were measured before and during treatment with either vitamin D2 or D3, 4,000 IU daily for 24 weeks. The results showed a distinct difference in the action of the two vitamins on bone metabolism during anticonvulsant treatment. The bone mass increased during treatment with vitamin D2, whereas the vitamin D3-treated patients showed unchanged values of bone mass, but an increased excretion rate of calcium, probably caused by increased intestinal calcium absorption. The data demonstrate that vitamins D2 and D3 (or their metabolites) have quantitative different effects in patients treated with phenobarbitone/phenytoin.