Combined treatment of growth hormone and the bisphosphonate pamidronate, versus treatment with GH alone, in GH-deficient adults: the effects on renal phosphate handling, bone turnover and bone mineral mass

OBJECTIVE A potential drawback of GH replacement therapy In GH deficient (GHD) patients is the Initial decrease in bone mass. The present study Investigates the effects of the addition of pamidronate to GH replacement therapy in adult GHD subjects, on serum PTH and 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃) levels, renal phosphate handling, bone turnover and bone mineral content (BMC). DESIGN Six GHD adult patfents were studied for two periods of 6 months with a wash-out period of 3 years. In the first period they were treated with conventional replacement therapy and GH. In the second study period GH treatment was Identical, whlle after 2 weeks 150 mg pamidronate per day was added. RESULTS In the first study period (GH only) there was a slgniflcant increase of phosphate reabsorption, without a change In serum PTH and 1,25-(OH)2D3 levels. Thls suggests a specific effect of GH or IGF-l on renal phosphate handling. This was supported by the close correlatlon between serum IGF-I levels and TmPlGFR (r=0·75, P < 0.0001). When GH was administered together with pamldronate, this correlation was less, but remained signiflcant (r=0·44, P < 0001). The Increase In bone turnover and decrease in BMC, as Initially observed during GH replacement therapy alone, were attenuated by simultaneous pamidronate administration. The decline in lumbar spine BMC (measured with dual-photon absorptiometry) at 6 months was ?3.1 ± 1.5% during GH replacement therapy alone vs an increase of +3.8 ± 2.0% during the admlnistratlon of the comblnatlon of GH and pamldronate (measured with dual-energy X-ray absorptlometry). At the distal and proximal forearm the changes amounted to ?0.5 ± 3.4% vs +4.5 ± 1.8% and ?1 ± 1.2% vs +1.2 ± 1.1 % respectively. CONCLUSIONS This study shows that the addition of a bisphosphonate to GH replacement therapy in GHD adults counteracts the GH (or IGF-I) Induced Increase In renal phosphate reabsorptlon. Furthermore, It reduces OH induced bone turnover and prevents the lnitlal decrease in bone mineral content seen during GH treatment alone, resultlng In a beneflclal effect on bone mlneral mass. Pamidronate might therefore be an important adjunct to GH replacement therapy in adults with GHD and severe osteopenia during the early phase of GH Induced stlmulation of bone turnover.     

Two years of treatment with recombinant human growth hormone increases bone mineral density in men with idiopathic osteoporosis

We have investigated the effects of GH treatment on bone turnover, bone size, bone mineral density (BMD), and bone mineral content (BMC) in 29 men, 27-62 yr old, with idiopathic osteoporosis. The patients were randomly assigned to treatment with GH, either as continuous treatment with daily injections of 0.4 mg GH/d (group A, n = 14) or as intermittent treatment with 0.8 mg GH/d for 14 d every 3 months (group B, n = 15). All patients were treated with GH for 24 months, with a follow-up period of 12 months, and also received 500 mg calcium and 400 U vitamin D3 daily during all 36 months. Fasting morning urine and serum samples were obtained for assay of IGF-I, bone markers, and routine laboratory tests at baseline, after 1, 12, 24, and 36 months. Body composition, BMD, and BMC were determined by dual-energy x-ray absorptiometry at baseline and every 6 months. After 2 yr, there was an increase in BMD in lumbar spine (by 4.1%) in group A, and in total body (by 2.6%) in group A and (by 2.7%) in group B. BMC of the total body and lean body mass increased, whereas fat mass decreased in both treatment groups. After 36 months, the BMD and BMC in lumbar spine and total body had increased further in both groups. We conclude that 2 yr of intermittent or continuous treatment with GH in men with idiopathic osteoporosis results in an increase in BMD and BMC that is sustained for at least 1 yr post treatment.     

Gender differences in the effects of long term growth hormone (GH) treatment on bone in adults with GH deficiency.

We recently observed that among patients with GH deficiency due to adult-onset hypopituitarism, men responded with a greater increase in serum levels of insulin-like growth factor I (IGF-I) and biochemical markers of bone metabolism than women when the same dose of recombinant human GH (rhGH) per body surface area was administered for 9 months. In the present study, 33 of the 36 patients in the previous trial (20 men and 13 women) continued therapy for up to 45 months. The dose of rhGH was adjusted according to side-effects and to maintain serum IGF-I within the physiological range. This resulted in a significant dose reduction in the men; consequently, the women received twice as much rhGH as the men (mean +/- SD, 1.9 +/- 1.1 vs. 1.0 +/- 0.6 U/day; P < 0.01). The increases in serum IGF-I levels and serum biochemical markers of bone metabolism were similar in men and women with these doses. The total bone mineral content (BMC) was increased after 33 and 45 months of treatment up to 5.1% (P = 0.004 and 0.0001). Bone mineral density (BMD), BMC, and the area of the femoral neck and the lumbar spine were also significantly increased after 33 and 45 months of treatment. When analyzed by gender, total body BMC, femoral neck BMD and BMC, and spinal BMC were significantly increased in males, but not in females (P < 0.05-0.01). In conclusion, rhGH treatment continued to have an effect on bone metabolism and bone mass for up to 45 months of therapy. The changes in bone mass were greater in the men, although they received lower doses of rhGH than the women. The results indicate that the sensitivity to GH in adult patients with GH deficiency is gender dependent.     

Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males*

OBJECTIVE In view of the fact that GH-deficient adults present with pronounced osteopaenia and can be considered at risk for osteoporotic fractures, we wanted to investigate the effects of biosynthetic GH replacement therapy (0.25 IU/kg/week) on biochemical indices of bone turnover and on bone mineral content (BMC) in a group of GH-deficient adult males. DESIGN We performed a 6-month randomized, double-blind, placebo-controlled study, followed by 12–24 months of GH treatment in all patients. PATIENTS Twenty adult males with GH deficiency of childhood onset were studied. MEASUREMENTS We measured serum IGF-I, serum phosphate, biochemical indices of bone turnover (serum alkaline phosphatase activity, serum osteocalcin, serum carboxyterminal propeptide of type-I procollagen, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios) and bone mineral content, measured at the forearm and the lumbar spine by single and dual-photon absorptiometry respectively. RESULTS After 3 and 6 months of GH administration, the serum levels of alkaline phosphatase, osteocalcin and carboxyterminal propeptide of type-I procollagen, and the fasting urinary hydroxyproline/creatinine ratio were significantly increased compared to placebo-treated patients (P<0.01 to P<0.001). During the open study phase, the values for these indices of bone turnover remained elevated above pretreatment levels (P<0 01 to P<0 001 at 12 months), a downward trend becoming apparent after about one year of GH treatment. BMC values showed an initial decline after 3 months of GH treatment (most likely due to an expansion of the remodelling space), followed by a significant and progressive increase above pretreatment values, reaching 7–8% for total BMC at the lumbar spine (L2-L4) and 9–9% for total BMC at the forearm, after 30 months of GH administration. CONCLUSIONS The data of our study show that administration of substitutive doses of growth hormone to GH-deficient adult males activates bone turnover for a period of at least one year and suggests that this may have a beneficial effect on bone mass in these patients.     

Changes in bone mineral and body composition following coronary artery bypass grafting in men

This study investigated bone mineral and body composition changes after coronary artery bypass grafting (CABG) in men. Twenty-six men 50 to 79 years of age underwent CABG for multivessel coronary disease. Dual-energy x-ray absorptiometry was performed before surgery and 3 months and 1 year after treatment to assess bone mineral content (BMC), bone mineral density (BMD), and body composition. Through 3 months after treatment, BMD decreased at the total body, arms, and pelvis. BMC of the arm decreased and losses at the total body and legs approached significance. Fat-free mass decreased in the arms and total body but not in the legs. Neither total body nor regional fat mass changed. At the 1-year follow-up visit, 15 of the initial 26 subjects returned for dual-energy x-ray absorptiometry. Compared with before treatment, BMD decreased at the total body and legs, whereas losses at the arms approached significance. Arm BMC decreased over the 1-year post-treatment period. No changes were observed in body composition. In conclusion, CABG and the ensuing convalescence period results in considerable arm bone mineral losses through 1 year after treatment.     

Importance of estrogen on bone health in Turner syndrome: a cross-sectional and longitudinal study using dual-energy X-ray absorptiometry

Osteoporosis and fractures are features in adults with Turner syndrome (TS). Using dual-energy x-ray absorptiometry, correcting bone mineral content (BMC) for height and lean mass (LTM) avoids misclassification of short children as osteopenic. Total body (TB), lumbar spine (LS), and femoral neck (FN) dual-energy x-ray absorptiometry scans were performed on 83 patients with TS (aged 4-24 yr). A prepubertal subgroup (n = 17) receiving GH was followed for 24 months. Age z-scores for height, TB BMC, LTM, the BMC/LTM ratio, and LS volumetric bone mineral density (vBMD) decreased significantly (P < 0.001) with age in prepubertal subjects (n = 51) but were constant in the combined pubertal and postmenarchal group (n = 32). Osteopenia was found in 14.5% (TB), 15.8% (LS), and 28.4% (FN) of patients. In the longitudinal subgroup, TB BMC z-scores decreased by -0.28 (0.31) in subjects remaining prepubertal (n = 11) but increased by 0.71 (0.56) in subjects entering puberty (n = 6; P = 0.007). The z-scores for height and LTM increased in both groups. Our results show a height-independent prepubertal decrease in bone mass accrual, which ceased with puberty. Optimizing bone mass in TS may require earlier induction of puberty than currently recommended. However, reduced FN volumetric bone mineral density and a dissociation of bone and muscle measures were age independent, suggesting an additional intrinsic bone defect.     

Further increase in forearm cortical bone mineral content after discontinuation of growth hormone replacement

OBJECTIVE Growth hormone replacement of adults with childhood onset GH deficiency results In an Increase In bone mineral density (BMD) after 6-12 months of OH replacement. By measuring BMD 12 months after discontinuation of GH replacement we aimed to Investigate whether there is an effect of GH replacement on BMD persisting after GH has been withdrawn. DESIGN BMD was measured 13 ± 1 (mean ± SE, range 11-16) months after discontinuation of OH replacement. PATIENTS Ten adults, age 23·;2 ±1·;4 (range 18·8-32·4) years, with childhood onset isolated GH deficiency (2 idiopathic, 8 irradiation induced) who had previously completed a study of the effect of 12 months of OH replacement on BMD. MEASUREMENTS Forearm cortical bone mineral content (BMC) was measured using single-photon absorptlometry at the proximal site of the distal forearm. Forearm integral BMC at the ultradistal site of the forearm and bone width at both proximal and ultradistal rites of the distal forearm were measured by the same technique. Vertebral trabecular BMD was measured using quantitative computed tomography. RESULTS Forearm cortical BMC was significantly greater than that measured at the time of discontinuation of OH (1·48 ±0·04 vs 1·44 ± 0·05 g/cm). There was no significant change in forearm integral BMC or in vertebral trabecular BMD after discontinuation of OH. There was no significant change in bone width at proximal and ultradistal sites of the distal forearm after discontinuation of GH. CONCLUSION After discontinuation of OH replacement the further increase In forearm cortical bone mineral content without a significant Increase In forearm bone width suggests that the Increase In cortical bone mineral content Is due to a persisting effect of previous GH replacement, and not to further spontaneous attainment of bone mass before peak bone mass lo reached. These findings emphasize the importance of continuing to monitor bone mass after the stimulus to Increase bone turnover has been withdrawn.     

The effect of cessation of growth hormone (GH) therapy on bone mineral accretion in GH-deficient adolescents at the completion of linear growth

In many countries, treatment of childhood-onset GH deficiency (GHD) with GH ceases when linear growth is complete. Peak bone mass occurs several years after the completion of linear growth. Given that GH has important anabolic actions on bone, discontinuation of GH therapy at the completion of linear growth may have adverse consequences for the attainment of peak bone mass in adolescent GHD patients. In this United Kingdom multicenter study, 24 adolescents (13 males, mean age 17.0 +/- 1.4 yr, SD) with severe GHD were randomized to discontinue or continue GH (0.35 IU/kg x wk) at the completion of linear growth. Whole body bone mineral content (BMC) and lumbar spine bone mineral density were assessed by dual-energy x-ray absorptiometry at baseline and then at 6-month intervals for 1 yr. Markers of bone remodeling (serum bone-specific alkaline phosphatase and urinary deoxypyridinoline) were measured at the same time points. In patients who continued GH (GH+), median BMC increased by 3.8% (interquartile range, 2.6, 5.9, P < 0.001) at 6 months; and by 6.0% (3.7-9.1, P < 0.001) at 12 months. In patients who discontinued GH (GH-) median BMC was unchanged at 6 and 12 months (+1.9%, -0.4-4.2, P = 0.9; and +2.4%, 0.4-4.9, P = 0.5, respectively, median, interquartile range). The differences in median change in BMC between the two groups at 6 and 12 months was marginally significant (P = 0.085 and 0.074, respectively). Mean lumbar spine bone mineral density increased by 4.7 (95% confidence interval, 1.0, 8.2) at 12 months in patients continuing GH (P = 0.01), but the mean change was not statistically significant change in patients who discontinued GH [+2.7% (95% confidence interval, -0.8, +6.2)]. These preliminary data suggest that, in adolescent patients with severe GHD, discontinuation of GH at completion of growth may limit the attainment of peak bone mass in this patient group. This may predispose to clinically significant osteopenia in later adult life.     

A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis

OBJECTIVE: To explore early changes and predictors of bone mass in children with juvenile idiopathic arthritis (JIA) in order to identify patients who will develop bone mass reductions. METHODS: We conducted a prospective cohort study of 108 children with early JIA (ages 6-18 years; mean disease duration 19.3 months) who were individually matched with 108 healthy children for age, sex, race, and county of residence. Bone mass and changes in total body, spine, femur, and forearm bone mineral density and bone mineral content (BMC), body composition, growth, and biochemical parameters of bone turnover were examined at baseline and at followup a mean of 24 months later. Low bone mass was defined as a Z score >1 SD below the reference population. RESULTS: Of the 200 children evaluated at followup, the 100 healthy children had greater gains in total body BMC (P = 0.035), distal radius BMC (P < 0.001), and total body lean mass (P < 0.001) than did the 100 JIA patients. Low or very low total body BMC was observed in 24% of the patients and 12% of the healthy children. Bone formation, bone resorption, and weight-bearing activities were reduced in the patients compared with the healthy children. Multiple regression analysis showed that in patients with JIA, serum bone-specific alkaline phosphatase, serum C-telopeptide of type I collagen, and weight-bearing activities were independent predictors of changes in total body BMC. Total body BMC was lower in patients with polyarticular onset than in those with oligoarticular disease onset. CONCLUSION: Patients with JIA have moderate reductions in bone mass gains, bone turnover, and total body lean mass early in the disease course.     

Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset.

In order to determine whether growth hormone (GH) deficiency of childhood onset affects the adult bone mineral status, we assessed bone mineral content (BMC) by photon absorptiometry in 30 full-grown GH-deficient men (8 with isolated GH deficiency and 22 with multiple pituitary deficiencies; 28 previously treated with GH) and in 30 male controls matched for age (within 4 yr) and height (within 10 cm). Forearm BMC was measured by single photon absorptiometry just proximally of the distal one third of the nondominant forearm (PBMC-2 in arbitrary units and PBMC/bone width (BW) after normalization for bone width) and at a more distal site, close to the carpal joint (DBMC-2 and DBMC/BW). Lumbar BMC was measured by dual photon absorptiometry and reported as total BMC for L2-L4 (LBMC in g) and after normalization for projected area (LBMD in g/cm2). The patients had a significantly lower BMC, both at the forearm (P less than 0.0001) and at the lumbar spine (P less than 0.005): 35.7 +/- 1.0 vs. 50.0 +/- 1.6 and 36.9 +/- 1.2 vs. 52.8 +/- 1.9 (mean +/- SEM) for PBMC-2 and DBMC-2 in patients and controls, respectively; 1.36 +/- 0.03 vs. 1.70 +/- 0.04 and 1.07 +/- 0.03 vs. 1.35 +/- 0.04 for PBMC/BW and DBMC/BW; 34.00 +/- 1.08 vs. 42.02 +/- 1.27 g for LBMC and 0.886 +/- 0.016 vs. 0.976 +/- 0.018 g/cm2 for LBMD. Both the patients with isolated GH deficiency and the patients with multiple pituitary deficiencies were osteopenic when compared to their respective controls (P less than 0.01 to P less than 0.0001 for the patients with multiple deficiencies; statistical significance reached for PBMC-2, DBMC-2, and DBMC/BW only, P less than 0.05, in the small group of patients with isolated GH deficiency). For the patients (n = 19) who had at least three serial measurements over a period of 6 to 28 months, no decrease in BMC was detected. Our findings indicate that men with GH deficiency of childhood onset present with a low adult bone mass, despite prior GH substitution in most of these subjects. The observations of a more pronounced bone mineral deficit at the forearm (20-30% lower mean values, depending on the type of measurements) than at the lumbar spine (9-19%) and the findings of osteopenia in both the patients with isolated GH deficiency and multiple pituitary deficiencies, support the view that GH deficiency per se is responsible for part of the observed deficit.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influence of orlistat on bone turnover and body composition

OBJECTIVE: To investigate the influence of the pancreas lipase inhibitor orlistat (OLS) on calcium metabolism, bone turnover, bone mass, bone density and body composition when given for obesity as adjuvant to an energy- and fat-restricted diet. DESIGN: Randomized controlled double-blinded trial of treatment with OLS 120 mg three times daily or placebo for 1 y. SUBJECTS: Thirty obese subjects with a mean body mass index (BMI) of 36.9+/-3.7 kg/m(2) and a mean age of 41+/-11 y. Sixteen patients were assigned to OLS and 14 to placebo. MEASUREMENTS: Dual energy X-ray absorptiometry (DXA) measurements of bone mineral and body composition included total bone mineral content (TBMC), total bone mineral density (TBMD), lumbar spine BMC and BMD, forearm BMC and BMD, fat mass (FM), fat free-mass (FFM), percentage fat mass (FM%) as well as a DXA estimate of the body weight. Body composition (FM, FFM and FM%) was estimated by total body potassium (TBK). Indices of calcium metabolism and bone turnover included serum values of ionized calcium (Ca(++)), iPTH (parathyroid hormone), alkaline phosphatase, 25(OH)-vitamin D, 1,25(OH)(2) vitamin D and osteocalcin as well as fasting urinary ratios of hydroxyproline/creatinine and Ca/creatinine (fU-OHpr/creat, fUCa/creat). RESULTS: There were no significant differences between OLS and placebo groups as to any of the body composition variables (FFM, FM, FM%) at baseline or after 1 y treatment. Weight loss was of 11.2+/-7.5 kg in the OLS group and 8.1+/-7.5 kg in the placebo group (NS). The changes in FM and FM% were significant in both groups determined by DXA as well as by TBK, but the group differences between these changes were not significant. The composition of the weight loss was approximately 80% fat in both groups. FFM only changed significantly by DXA in the OLS group (-1.3 kg), but the difference from the placebo group was not significant. Forearm BMD in both groups, forearm BMC in the OLS group and TBMD in the placebo group fell discretely but significantly, but there were no significant group differences between the OLS and the placebo-treated group. All biochemical variables except s-osteocalcin changed significantly after 1 y in the OLS group, disclosing a pattern of an incipient negative vitamin D balance, a secondary increase in PTH-secretion, and an increase in bone turnover with the emphasis on an increase in resorption parameters (fU-OHpr/creat, fUCa/creat). In the placebo group, only s-25(OH)vitamin D and fU-OHpr/creat changed significantly, but the pattern was also that of a deteriorated vitamin D status and an increase in PTH levels and bone turnover. The only biochemical variable which was significantly different between OLS and placebo groups after one year was the fU-OHpr/creat ratio, which increased from 12.0 to 20.1 in the OLS group but only from 10.9 to 1 3.2 in the placebo group. CONCLUSION: One year's treatment with OLS induces a lipid malabsorption which enhances a dietary weight loss without any significant deleterious effects on body composition. OLS induces a relative increase in bone turnover in favour of resorption, possibly due to malabsorption of vitamin D and/or calcium. However, no changes in bone mass or density are seen after 1 y of OLS treatment apart from those explained by the weight loss itself. Thus 1 y of OLS treatment seems safe from a 'bone preserving' point of view. A vitamin D and calcium supplement should be taken during the treatment.     

Bone development during GH and GnRH analog treatment

Estrogens, GH and IGFs are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. Treatment of precocious puberty with GnRH analogs (GnRHa), by reducing sex steroid levels, leads to a situation of hypoestrogenism that may theoretically have a detrimental effect on bone mass during pubertal development. A reduction in bone mineral density (BMD) during GnRHa treatment has been demonstrated, but GnRHa treatment in patients with central precocious puberty (CPP) does not seem to impair the achievement of normal peak bone mass (PBM) at final height. However, calcium supplementation is effective in improving bone densitometric levels and may promote better PBM achievement. In children and adolescents with GH deficiency (GHD), BMD assessed by dual-energy X-ray absorptiometry (DEXA) and bone turnover are significantly reduced, but they are stimulated by GH treatment. GH treatment leads to improved bone density, function of the dose and duration of treatment, and patients may require prolonged GH treatment beyond the time of growth to improve PBM. After the discontinuation of GH therapy, the more active population had higher bone mineral content (BMC) levels than patients with low physical activity. In our experience, the therapeutic association of GH and calcium also represents a valuable tool in pursuing a proper BMC in GHD patients. We concluded that nonhormonal factors, such as physical activity and nutritional factors, are important in determining bone metabolism and bone mass.     

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 2.1% 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 less than 0.05). 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.     

Body composition and bone mineralization measurement in calves of different genetic origin by using dual-energy X-ray absorptiometry

The purpose of this study was to investigate the differences in bone mineralization [bone mineral density (BMD, g/cm(2)), and bone mineral content (BMC, %)] and body composition of F1 and F2 crossbred calves and their purebred controls from the dairy breeds German Holsteins (GH) and German Fleckvieh (FV). In total, 62 male and 64 female calves were analyzed under light sedation with dual-energy X-ray absorptiometry (DXA). The study started when the calves were 4 days old and continued until they were 60 days old. GH calves had a significantly lower BMD than all other lines-with the highest BMD and BMC in the FV male symbol x F1 female symbol line. Since the average BMD of the F1 calves was higher than the average BMD of their parents, a small heterosis effect for this trait seems likely. The absolute differences in soft tissue composition were small with a slightly higher average fat content for F1 calves compared with the parent breeds.     

Relationship between Local and Total Bone Mineral Content after Gastric Surgery

We compared the total body bone mineral mass (TBBM), assessed by the dualphoton technique, with the local bone mineral mass (BMC), measured by single- photon absorptiometry, in 27 ulcus patients treated by either gastric resection or parietal cell vagotomy. Except for raised concentrations of serum alkaline phosphatase in the Billroth I resection group, the biochemical findings and the measurements of bone mass (local and total) were normal. A highly significant correlation between local and total body bone mineral mass was found in both patients (r = 0.84) and controls (r = 0.91). Since the relationship between these two measurements is identical in the patient population and in the age-matched control group, it is concluded that the local BMC may be useful to estimate total bone mass after gastric surgery.     

Relationship between local and total bone mineral content after gastric surgery

We compared the total body bone mineral mass (TBBM), assessed by the dual-photon technique, with the local bone mineral mass (BMC), measured by single-photon absorptiometry, in 27 ulcus patients treated by either gastric resection or parietal cell vagotomy. Except for raised concentrations of serum alkaline phosphatase in the Billroth I resection group, the biochemical findings and the measurements of bone mass (local and total) were normal. A highly significant correlation between local and total body bone mineral mass was found in both patients (r = 0.84) and controls (r = 0.91). Since the relationship between these two measurements is identical in the patient population and in the age-matched control group, it is concluded that the local BMC may be useful to estimate total bone mass after gastric surgery.     

Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

OBJECTIVE: To evaluate the effect of physiological adult growth hormone (GH) replacement on bones. DESIGN: Thirty-six prospective severely growth hormone-deficient (GHD) adults (22 females and 14 males) were randomised to either 18 months of GH (0.03 mU/kg/day) or placebo treatment. METHODS: Bone mineral density and content (BMD, BMC) and body composition were evaluated by dual energy X-ray absorptiometry at baseline and after 6, 12 and 18 months. Serum concentrations of insulin-like growth factor-I (IGF-I), IGF binding protein 3, osteocalcin, carboxyterminal propeptide of type I collagen, carboxyterminal crosslink telopeptide of type I collagen, amino-terminal propeptide of type III procollagen and urine pyridinolin and deoxypyridinolin were determined. RESULTS: IGF-I levels increased from 63.2 microg/l (+/-10.1) to 193.6 (+/- 25.8) microg/l (mean (+/-s.e.)) (P<0.001 compared with placebo). Markers of bone turnover increased significantly from 142% to 227% of baseline values (all P<0.001 compared with placebo). Body composition changes were an increase of lean body mass and a decrease of fat mass resulting in a reduction of percentage body fat of +/- 1.8 (+/- 3.8) in the GH-treated group vs an increase of 1.0 (+/-2.9)) in the placebo-treated group (P=0.002). CONCLUSIONS: No significant difference in BMD or BMC between the GH and placebo groups was found after 18 months. At several sites the variances of changes from baseline were significantly greater in the GH than in the placebo group, indicating an impact of the treatment. From baseline to 6 months an insignificant reduction of total BMD was seen while an increase of BMD was found from 6 to 18 months in the GH group compared with the placebo group.This placebo-controlled trial confirmed the longer term open studies on the effect on bones in patients with GHD, with an initial overrepresentation of bone resorption followed by an increase in BMD which at 18 months had reached baseline level.     

The effect of glucocorticoids on bone mass in rheumatoid arthritis patients. Influence of menopausal state

We studied 97 patients with definite or classic rheumatoid arthritis (RA). Fifty-four patients (19 premenopausal women, 25 postmenopausal women, and 10 men) had been treated with low-dose glucocorticoids for at least 12 months (mean dose less than 10 mg/day). The remaining 43 patients (15 premenopausal women, 17 postmenopausal women, and 11 men) had been treated with penicillamine, and served as a patient control group. The distal forearm bone mineral content (BMC) was measured in all patients by single photon absorptiometry using 125I, and the total body bone mineral (TBBM) was measured in 61 patients by dual photon absorptiometry using 153Gd. Compared with normal controls, both treatment groups had significantly decreased BMC and TBBM (0.01 less than P less than 0.001). When the patients were stratified according to pre- and postmenopausal state, we found significantly lower BMC and TBBM values in the premenopausal glucocorticoid-treated women than in penicillamine-treated women. However, no differences in BMC and TBBM values were found in the corresponding postmenopausal groups. In the premenopausal women treated with glucocorticoids, the duration of treatment and cumulative dose correlated with BMC. No such correlations were found in the postmenopausal women. We conclude that 1) RA is associated with loss of bone mass, 2) systemic glucocorticoid treatment further aggravates the bone loss, 3) in postmenopausal RA patients, the bone loss resulting from menopause and from the disease itself is not accelerated by low-dose glucocorticoids, and 4) in premenopausal RA patients, however, the bone mass is significantly affected by glucocorticoid treatment. We therefore suggest that these factors be considered when prescribing glucocorticoids, in order to minimize the bone loss.     

Body composition of prolactin-, growth hormone,and thyrotropin-deficient Ames dwarf mice

Ames dwarf mice have primary deficiency of prolactin (PRL), growth hormone (GH), and thyroid-stimulating hormone (TSH), and live considerably longer than normal animals from the same line. In view of the documented effects of GH, PRL, and thyroid hormones on lean and fat body mass and skeletal growth, and the suspected relationship of body size and composition to life expectancy, it was of interest to examine agerelated changes in body composition of Ames dwarf mice. Lean mass, fat mass, bone area, and bone mineral content (BMC) were determined in dwarf and normal mice at the ages of 2, 4.5–6, and 18 mo using dual X-ray absorptiometry. In addition to the expected significant declines in lean mass, bone area, and BMC, dwarf mice exhibited attenuation of the age-related increase in bone mineral density and delayed or attenuated increase in percentage of body fat. Percentage of body fat was lower in adult dwarfs than in the corresponding normal controls. Patterns of age-related changes in body composition in Ames dwarf mice are consistent with the recent report of age-related changes in body composition in PRL receptor knockout mice. We suspect that reduction in relative adiposity may contribute to the previously reported increase in insulin sensitivity of Ames dwarf mice and thus may be a factor in delayed aging and increased longevity of these animals.     

17 Beta-estradiol and continuous norethisterone: a unique treatment for established osteoporosis in elderly women

Forty women aged 64.7 +/- 5.1 yr with established postmenopausal osteoporosis were blindly allocated to 1 yr's treatment with either continuous combined estrogen/progestogen therapy (2 mg estradiol + 1 mg norethisterone acetate + 500 mg calcium daily) or placebo + 500 mg calcium daily. In the group treated with hormones bone mineral density in the spine (dual photon absorptiometry) and bone mineral content in the ultradistal forearm (single photon absorptiometry) increased highly significantly by 8-10% during the 1 yr of treatment. Bone mineral content in the mid-shaft of the forearm (single photon absorptiometry) and the total body bone mineral (dual photon absorptiometry) increased by 3-5% when compared to that in the placebo group, which showed virtually unchanged values at all measurement sites. Seven of the women treated with hormones were examined after a further year of treatment. BMC increased by another 3-6%, reaching a 12% increase in bone mineral density in the spine after 2 yr of treatment. Biochemical estimates of bone resorption (fasting urinary calcium and hydroxyproline) and bone formation (serum alkaline phosphatase and plasma osteocalcin), decreased significantly (P less than 0.001) in the group treated with hormones, but remained unchanged in the placebo group. The reduction in indices of bone resorption was more pronounced than that in bone formation after one year, indicating a positive bone balance. No further changes were seen in these bone turnover parameters during the second year of treatment. In the group treated with hormones, serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol decreased by about 12% (P less than 0.05-P less than 0.01), whereas high density lipoprotein cholesterol decreased by about 8% (P less than 0.001). The high density lipoprotein cholesterol/low density lipoprotein cholesterol ratio was unchanged. The hormone treatment did not produce any major side effects, and only minor bleedings were experienced by a few women. The present study demonstrates that treatment with female sex hormones in this particular combination is a realistic approach to the treatment of women with established postmenopausal osteoporosis.