T. B. Hansen

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women — results of the Danish Osteoporosis Prevention Study

OBJECTIVES To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. RESULTS After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years. CONCLUSIONS It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.

Cross calibration of QDR-2000 and QDR-1000 dual-energy X-ray densitometers for bone mineral and soft-tissue measurements

Replacement of dual energy X-ray densitometry (DXA) equipment may be necessary in many labs with time, or new equipment may be added. In this context we compared patient scans between a Hologic QDR-1000W and a QDR-2000 (n = 29-43, depending on anatomic region) and between QDR-2000 single beam (SB) and fan beam (FB) modes (n = 40-62) as a quality control measure. A total of 83 subjects (79 females and four males) with a wide range of bone mineral densities (BMD) were studied. There was a linear relationship between results with the QDR-1000W and QDR-2000 in SB mode, and between SB and FB mode on the QDR-2000, but the magnitude of the coefficients and constants differed for the different anatomic regions. In SB mode the QDR-2000 underestimated whole body and forearm BMD by 3% relative to the QDR-1000W, even after cross calibration using a spine phantom. Femoral total BMD was slightly, but not significantly, underestimated. Thus, additional postanalysis correction had to be applied to forearm and whole-body scans. In FB with the QDR-2000, spine and whole-body BMD was underestimated by 3%, but femur total and neck BMD was overestimated by 2.2 and 2.8%, respectively, compared with SB scans on the same device. Soft-tissue composition with FB (enhanced analysis protocol) on the QDR-2000 differed greatly from that obtained using SB (standard protocol). Lean tissue mass was 4 kg lower and fat mass 4 kg higher in FB mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition

OBJECTIVE Studies with GH substitution in GH‐deficient (GHD) adults lasting more than 6 months have so far been uncontrolled. End‐points such as physical fitness and body composition may be subject to a considerable placebo effect which weakens the validity of open studies. We therefore tested GH (2 IU/m2 per day) versus placebo treatment for 12 months.

Site of osteodensitometry in perimenopausal women : Correlation and limits of agreement between anatomic regions

Because the bone mineral density (BMD) in different anatomic regions is heterogenous the number of women who fulfill the World Health Organization definition of osteopenia or osteoporosis increases with the number of regions examined. The purpose of this study was to investigate the agreement between measurements of the spine, femur, forearm, and whole body following menopause. Two thousand and five healthy, perimenopausal women, mean age 50.6 years, were studied using Hologic QDR‐1000/W and QDR‐2000 densitometers. Though the BMD of different anatomic regions were correlated (r = 0.40–0.77, p < 0.01), the variability in each patient regarding T and Z scores between regions was considerable. For example, despite a high correlation (r = 0.67, p < 0.01) and no systematic difference between the T scores for total femoral and lumbar BMD, the limits of agreement (mean difference ± 2 SD) for the comparison were −1.89 to 1.87. Femoral neck T scores were 0.5 SD lower than those of the other regions, confirming reports that the young adult reference for this measurement is disproportionally high. The prevalence of osteoporosis was 1.2% when femur total BMD was considered alone and 5.9% when lumbar and ultradistal forearm results were included. However, as many as 7.9% showed osteoporosis of the femoral neck when the Hologic T score was used, compared with 0.7% using National Health and Nutrition Examination Survey (NHANES) values. The choice of anatomic region and availability of appropriate young adult reference data has considerable impact on the apparent prevalence of osteoporosis. Given the heterogeneity between regions, a combination of spinal and femoral densitometry should be used in diagnosing osteoporosis, though this increases the prevalence of osteoporosis by 50% or more in perimenopausal women.

Determinants of serum insulin-like growth factor I in growth hormone deficient adults as compared to healthy subjects

Growth hormone status is an important determinant of serum IGF‐I but it is well known that hypopituitary adults with pronounced GH‐deficiency (GHDA) may exhibit normal IGF‐I levels. To elucidate possible causes of this apparent paradox we compared the significance of putative IGF‐I predictors in GHDA and normal subjects.

The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with concomitant reductions in adiposity. A 12 month placebo-controlled study

OBJECTIVE: To investigate whether the changes in lipoproteins following growth hormone (GH) substitution in GH deficient (GHD) adults are determined by the concomitant changes in body composition and physical fitness in a controlled long-term study.DESIGN: A randomized, double-blind, placebo-controlled trial with GH (2 IU/m2) or placebo given for 12 months.SUBJECTS: Twenty-seven patients (18 male, 9 female, aged 21–61 y) with adult onset GH deficiency. Comparisons were made with age- and gender-matched healthy adults.MEASUREMENTS: Serum triglycerides (TG) and lipoproteins, body composition (Dual-Energy X-ray Absorptiometry and computerized tomography), and exercise capacity (V˙O2-max measured by bicycle ergometry) were measured at baseline and after 12 months.RESULTS: Baseline values of total cholesterol, low-density lipoprotein (LDL) and serum triglycerides were significantly higher in GHD adults compared to normal subjects (P<0.001, P<0.001, P=0.004, respectively) whereas no difference in high-density lipoprotein (HDL) or lipoprotein (a) (Lp(a)) was found. After one year of GH treatment total cholesterol decreased significantly (P=0.02). Serum LDL decreased after GH and increased after placebo, but the difference in delta values was not significant (P=0.12). Serum HDL and TG concentrations were unchanged. Lp(a) increased but not significantly. Serum total and LDL cholesterol remained significantly elevated after one year of GH treatment. Significant reductions in total and visceral adiposity, and improved exercise capacity were also recorded after GH treatment. In normal subjects, serum total cholesterol and TG correlated positively with age, subcutaneous fat and intraabdominal fat, and negatively with V˙O2-max. Serum LDL correlated positively with age. In GHD patients, baseline values of serum TG correlated positively with subcutaneous fat and serum insulin. During treatment, no significant correlations were found between the changes in lipoproteins and in body composition.CONCLUSION: The cholesterol lowering effect of GH is not determined by the concomitant decrease in adiposity, which supports the concept of a direct effect of GH on lipoprotein metabolism.

Whole body and regional soft tissue changes in growth hormone deficient adults after one year of growth hormone treatment: a double‐blind, randomized, placebo‐controlled study

OBJECTIVE Adults with GH deficiency (GHD) exhibit changes in body composition. Studies of the effects of GH substitution on body composition have been short‐term or not adequately controlled. The purpose of this study was to evaluate the long‐term effects of GH on soft tissue using dual‐energy X‐ray absorptlometry (DEXA). This technique enables assessment of whole body as well as regional soft tissue composition.

Growth Hormone Treatment in Adults with Adult‐Onset Growth Hormone Deficiency Increases Iliac Crest Trabecular Bone Turnover: A 1‐Year, Double‐Blind, Randomized, Placebo‐Controlled Study

The effects of growth hormone (GH) substitution on bone metabolism were evaluated by dynamic histomorphometry on iliac crest bone biopsies. Twenty‐nine patients, aged 21–61 years (mean 45.5 years), with adult‐onset GH deficiency (GHD) were randomized to receive subcutaneous injections with GH (2 IU/m2/day = 0.67 mg/m2/day) or placebo for 12 months. Serum insulin‐linke growth factor I (IGF‐I) levels increased 263 ± 98% (mean ± SD) during GH treatment (p < 0.0001). In the GH group, osteoid surface increased during treatment from 11% (3–15%) (median [25–75 percentiles]) to 21% (10–27%) (p = 0.01) and mineralizing surface from 4% (1–8%) to 11% (7–16%) (p = 0.04). Moreover, erosion surface tended to increase in the GH group from 2% (1–3%) to 4% (3–5%) (p = 0.07). The quiescent surface decreased in the GH group from 87% (83–96%) to 74% (68–87%) (p = 0.01). The adjusted appositional rate, mineral apposition rate, bone formation rate, bone erosion rate, mineralization lag time, and osteoid thickness remained unchanged during treatment Erosion depth showed a trend toward increase in the GH group (p = 0.09), whereas wall thickness was unchanged. Bone balance at the remodeling unit level and activation frequency were unchanged. At the tissue level, bone erosion rate increased significantly from 26% (17–36%)/year to 39% (23–72%)/year (p = 0.03). Similarly, the bone formation rate at the tissue level tended to increase, from 24% (15–31%)/year to 36% (17%‐63%)%/year (p = 0.06). Finally, bone balance at the tissue level decreased significantly from 1% (–2–2%)/year to −5% (−13–1%)/year (p = 0.01). No significant difference in change was seen in the cancellous bone volume. We conclude that 12 months of GH substitution therapy increases trabecular bone turnover. Moreover, our data suggest that bone balance at the bone multicellular unit level is not changed to positive. (J Bone Miner Res 2000;15:293–300)

Influence of Growth Hormone and Androgens on Body Composition in Adults

The secretion of both growth hormone (GH) and androgens declines with age which may play a role in the senescent changes in body composition and organ function. Among healthy adults abdominal adiposity is an important negative determinant of GH secretion. Surprisingly, abdominal or android obesity seems inversely correlated with testosterone levels in males but not in females. The ability of GH to promote lipolysis and preserve or increase lean body mass has been reappraised in substitution studies in GH-deficient adults. By comparison, adequately controlled studies of androgen replacement in hypogonadal and/or elderly males are few. In view of the physiological and clinical relevance of obtaining information about the aging process, there is a need for controlled experiments addressing similarities and differences between the action of GH and sex steroids in adults.

Body composition in active acromegaly during treatment with octreotide: a double‐blind, placebo‐controlled cross‐over study

OBJECTIVE In active acromegaly body composition is characteristically altered by an increase in lean body mass and a corresponding reduction in fat mass. These changes are induced by an excessive secretion of GH and insulin‐like growth factor I (IGF‐I). Growth hormone is an anabolic hormone and leads to stimulation of protein synthesis and an increased lipolysis in adipose tissue.