Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial

BACKGROUND: Despite the high prevalence of hypovitaminosis D in children and adolescents worldwide, the impact of vitamin D deficiency on skeletal health is unclear. METHODS: One hundred seventy-nine girls, ages 10-17 yr, were randomly assigned to receive weekly oral vitamin D doses of 1,400 IU (equivalent to 200 IU/d) or 14,000 IU (equivalent to 2,000 IU/d) in a double-blind, placebo-controlled, 1-yr protocol. Areal bone mineral density (BMD) and bone mineral content (BMC) at the lumbar spine, hip, forearm, total body, and body composition were measured at baseline and 1 yr. Serum calcium, phosphorus, alkaline phosphatase, and vitamin D metabolites were measured during the study. RESULTS: In the overall group of girls, lean mass increased significantly in both treatment groups (P < or = 0.05); bone area and total hip BMC increased in the high-dose group (P < 0.02). In premenarcheal girls, lean mass increased significantly in both treatment groups, and there were consistent trends for increments in BMD and/or BMC at several skeletal sites, reaching significance at lumbar spine BMD in the low-dose group and at the trochanter BMC in both treatment groups. There was no significant change in lean mass, BMD, or BMC in postmenarcheal girls. CONCLUSIONS: Vitamin D replacement had a positive impact on musculoskeletal parameters in girls, especially during the premenarcheal period.     

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.     

A prospective study of 5 years of GH replacement therapy in GH-deficient adults: sustained effects on body composition, bone mass, and metabolic indices

GH replacement therapy has proved its efficacy and safety in short-term trials and in a few long-term trials with limited number of subjects. In this 1-center study, including 118 consecutive adults (70 men and 48 women; mean age, 49.3 yr; range, 22-74 yr) with adult-onset GH deficiency, the effects of 5 yr of GH replacement on body composition, bone mass, and metabolic indices were determined. The mean initial GH dose was 0.98 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.48 mg/d. The mean IGF-I SD score increased from -1.73 at baseline to 1.66 at study end. A sustained increase in lean body mass and a decrease in body fat were observed. The GH treatment increased total body bone mineral content as well as lumbar (L2-L4) and femur neck bone mineral contents. BMD in lumbar spine (L2-L4) and femur neck were increased and normalized at study end. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. At 5 yr, serum concentrations of triglycerides and hemoglobin A(1c) were reduced compared with baseline values. The treatment responses in IGF-I SD score, body fat as estimated by four- and five-compartment body composition models, total body protein and nitrogen, and lumbar bone mineral content and BMD were more marked in men than in women. One patient died during the period, four patients discontinued the study due to adverse events, and one dropped out due to lack of compliance. Four patients were lost to follow-up. However, all patients were retained in the statistical analysis according to the intention to treat approach used. In conclusion, 5 yr of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A(1c) were first observed after years of treatment.     

Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial

CONTEXT: Recent studies have reported low bone mineral density (BMD) in HIV-infected patients. Annual iv administration of 4 mg zoledronate has been shown to increase BMD and suppress bone turnover in postmenopausal women. OBJECTIVE: The objective of the study was to determine whether annual administration of 4 mg zoledronate will increase BMD in HIV-infected men receiving highly active antiretroviral therapy. DESIGN AND SETTING: A 2-yr randomized placebo-controlled trial was conducted in a clinical research center. PARTICIPANTS: A total of 43 HIV-infected men were treated with highly active antiretroviral therapy for at least 3 months, with BMD T score less than -0.5. INTERVENTION: Participants received annual iv administration of 4 mg zoledronate or placebo. All participants took 400 mg/d calcium and 1.25 mg/month vitamin D. MEASUREMENTS: BMD at the lumbar spine, total hip and total body, and bone turnover markers were measured. RESULTS: At the lumbar spine, BMD increased by 8.9% over 2 yr in the zoledronate group compared with an increase of 2.6% in the control group (P<0.001). At the total hip, BMD increased by 3.8% over 2 yr in the zoledronate group compared with a decrease of 0.8% in the control group (P<0.001). At the total body, BMD increased by 2.3% over 2 yr compared with a decrease of 0.5% in the control group (P<0.001). Urine N-telopeptide decreased by 60% at 3 months in the zoledronate group and thereafter remained stable. CONCLUSIONS: Annual administration of zoledronate is a potent and effective therapy for the prevention or treatment of bone loss in HIV-infected men. The current data provide the first trial evidence of the BMD effects of annual zoledronate beyond 1 yr in any population, as well as being the first reported trial in men.     

Longitudinal analysis of bone mineral density in pre-menopausal female systemic lupus erythematosus patients: deleterious role of glucocorticoid therapy at the lumbar spine

OBJECTIVE: To evaluate whether bone loss occurs over time in pre-menopausal systemic lupus erythematosus (SLE) patients. METHODS: We performed a longitudinal bone mineral density (BMD) analysis in a group of 35 pre-menopausal female SLE patients. Lumbar spine and hip (total and sub-regions) BMDs were measured twice 21 +/- 11 (mean +/- S.D.) months apart by dual-energy X-ray absorptiometry. RESULTS: In the whole cohort of SLE patients, significant bone loss was observed at the lumbar spine (-1.22%/yr) but not at the total hip. Further analyses indicated that lumbar spine bone loss (-2.12%/yr) occurred exclusively in the subgroup of patients who had taken a mean prednisolone daily dose >7.5 mg between the two BMD measurements. Moreover, bone loss was more important in patients who had previously received a cumulative prednisolone dose 7.5 mg.     

Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women

Strenuously exercising young women with hypothalamic amenorrhea are hypoleptinemic and have low bone mineral density (BMD) and content (BMC), which predispose them to increased fracture risk. Short-term leptin replacement in these women corrects many neuroendocrine abnormalities and increases circulating levels of bone formation markers. Whether treatment with recombinant methionyl human leptin (metreleptin) for a long period improves BMD and BMC remains unknown. We studied 20 strenuously exercising young women with hypoleptinemia (leptin concentration <5 ng/mL) and hypothalamic amenorrhea of at least 6 months' duration. Eleven were randomized to metreleptin (initial dose, 0.08 mg/[kg·d] for 3 months; altered thereafter to 0.12 mg/kg for lack of efficacy or 0.04 mg/[kg d] for more than 5% weight loss) and 9 were randomized to placebo for 9 months. After a 3-month washout period, subjects were reexamined at the 1-year time point. Six subjects elected to continue on open-label metreleptin treatment for another 12 months. Two subjects dropped out after 18 months, and 4 completed the entire 2-year study. The BMD and BMC of the total body, lumbar spine (L1-L4), hip, and radius were assessed by using dual-energy x-ray absorptiometry at baseline and at 3, 6, 9, 12, 18, and 24 months of treatment. Metabolic and hormonal parameters and bone markers were measured in blood and urine. Metreleptin significantly increased BMC (P = .034) and tended to increase BMD (P = .069) at the lumbar spine at 9 months in the entire study group (intention-to-treat analysis). In subjects who completed the entire 2-year study (n = 4), metreleptin significantly increased BMD (P = .024) and BMC (P = .049) at the lumbar spine by 4% to 6%. Changes were not significant at the whole body, hip, and radius. Changes in hormonal and metabolic parameters and bone markers were moderate during the first year of treatment, but metreleptin further increased insulin-like growth factor 1 and decreased cortisol and cross-linked C-terminal telopeptide of type 1 collagen concentrations in serum during the second year of treatment (P < .05). The incremental area under the estradiol concentration curve over the 2-year course of the study correlated positively with the corresponding increase in lumbar spine BMD (ρ = 0.42, P = .039). Long-term metreleptin administration in strenuously exercising young women with hypothalamic amenorrhea and hypoleptinemia increases lumbar spine BMD and BMC and alters bone remodeling milieu to favor bone accretion. Results from this pilot study should be confirmed by future, larger clinical trials and need to be extended by studying bone microarchitecture and fracture risk.     

Dietary calcium intake protects women consuming oral contraceptives from spine and hip bone loss

CONTEXT: It is estimated that 80% of all women have used oral contraceptives (OCP), but OCP use may prevent attainment of maximal peak bone mass in young women and thus increase the risk of osteoporosis later in life. OBJECTIVE: This study examined whether increased calcium intake could reduce the detrimental effects of OCP use on bone mass in young women. DESIGN: The study design was a 1-yr intervention. SETTING: The study was performed in a general community setting. SUBJECTS: One hundred fifty-four young (18-30 yr old) healthy women with a dietary calcium intake of less than 800 mg/d began the study, and 135 completed the trial. Intervention: Subjects were randomly assigned to one of three diet intervention groups: 1) control, continuous established (<800 mg/d) dietary calcium intake; 2) medium dairy, increase calcium intake to approximately 1000-1100 mg/d; and 3) high dairy, increase calcium intake to approximately 1200-1300 mg/d. Randomization was stratified by OCP use. MAIN OUTCOME MEASURES: The main outcome measures were total body bone mineral density (BMD) and content (BMC); total hip BMD, BMC, and bone area; and spine BMD, BMC, and bone area. Results: Dairy product intervention positively impacted the percentage change in total hip BMD and BMC. In addition, dairy product intake prevented a negative percentage change in total hip and spine BMD in OCP users. CONCLUSION: Dairy product intake, at levels necessary to achieve the recommended intakes of calcium, protected the total hip BMD and spine BMD from loss observed in young healthy women with low calcium intakes who were using OCP.     

Bone mineral density, bone metabolism and body composition of children with chronic renal failure, with and without growth hormone treatment

OBJECTIVE: Osteopenia has been reported in adult patients with chronic renal failure (CRF). Only a few studies have been performed in children. The objective of this study was to evaluate bone mineral density (BMD), bone turnover, body composition in children with CRF and to study the effect of GH on these variables. DESIGN: Two groups were identified: patients with growth retardation who received GH (GH-group) and patients most of whom were not growth retarded who did not receive GH (no-GH-group). After an observation period of 6 months, the patients in the GH-group started GH treatment. Patients were studied every 6 months during 18 months. PATIENTS: Thirty-six prepubertal patients (27 boys and 9 girls), mean age 7.9 years, with CRF participated in the study. The GH-group consisted of 17 patients of whom 14 completed one year treatment. The no-GH-group consisted of 19 patients, of whom 16 were followed for 6 months, 14 for 12 months and 13 for 18 months. MEASUREMENTS: Lumbar spine BMD, total body BMD and body composition were assessed by dual energy X-ray absorptiometry, compared to age-and sex-matched reference values of the same population and expressed as standard deviation scores (SDS). BMD of appendicular bone was measured by quantitative microdensitometry (QMD). Blood samples were obtained to assess bone metabolism and growth factors. RESULTS: Baseline mean lumbar spine and total body BMD SDS of all patients were not significantly different from normal. Mean lumbar spine and total body BMD SDS did not change significantly in the GH-group during GH treatment. The change of QMD at the midshaft during the first 6 months of GH treatment was significantly smaller than during the observation period (P < 0.01). Height SDS and biochemical markers of both bone formation and bone resorption increased significantly during GH treatment; 1,25-dihydroxyvitamin D remained stable. Lean tissue mass increased (P < 0.001) and percentage body fat decreased (P < 0.01) during GH treatment. BMD, the biochemical markers of bone turnover which are independent of renal function, and body composition remained stable in the no-GH-group. CONCLUSIONS: Mean lumbar spine and total body BMD of children with chronic renal failure did not differ from healthy controls. The lack of a GH-induced increase in 1,25-dihydroxyvitamin D levels, probably due to treatment with alpha-calcidol, might be linked to the absence of a response in BMD during GH treatment in children with chronic renal failure.     

Effect of low-dose of recombinant human growth hormone on bone metabolism in elderly women with osteoporosis

BACKGROUND: There has been increasing evidence that the growth hormone (GH)-IGF-I axis plays an important part in the maintenance of bone mass. However, controversy still exists as to the effect of GH treatment on bone mineral density (BMD) in elderly patients with osteoporosis. OBJECTIVE: To investigate the effect of low-dose GH treatment on markers of body composition and bone turnover, serum concentrations of IGF-I and IGF-binding proteins (IGFBPs), and BMD at the radius and lumbar spine in eight elderly Japanese women with osteoporosis. METHODS: Participants were treated with GH as a single daily subcutaneous injection (0.125 IU/kg per week; 0.00595 mg/kg per day) for 48 weeks. RESULTS: Markers of bone formation and bone resorption were both increased up to 24 weeks of GH treatment. The bone formation markers remained increased during GH treatment, whereas the bone resorption markers returned to baseline values after 24 weeks of GH treatment. GH treatment caused a rapid (within 2 weeks) and sustained increase in serum IGF-I concentration. As for IGFBPs, serum concentrations of IGFBPs-2, -3 and -4 did not change significantly during GH treatment. In contrast, GH treatment caused a gradual increase in serum IGFBP-5 concentration, with a significant increase seen 48 weeks after the start of GH treatment. Radial BMD seemed to be increased during the late period of GH treatment, although the change was not significant. Lumbar BMD did not change during GH treatment. GH treatment caused a significant increase in hand grip strength. None of the GH-treated participants had new fractures and side effects such as edema and joint pain. Radial BMD was significantly increased after discontinuation of GH treatment for another 48 weeks and a similar tendency was observed at the lumbar spine (7.1+/-2.3% above pretreatment values for the radius and 3.6+/-2.0% for the lumbar spine). CONCLUSIONS: Low-dose GH treatment attenuated the decrease in muscle strength and bone mass in elderly women without side effects, although changes in nutrition and exercise might affect BMD. The present findings provide useful information regarding the use of low-dose GH treatment in elderly women with osteoporosis.     

The effect of short- and long-term growth hormone treatment on bone mineral density and bone metabolism of prepubertal children with idiopathic short stature: a 3-year study

OBJECTIVE: We recently reported that children with idiopathic short stature (ISS) have decreased lumbar spine bone mineral density (BMD) that increases after 1 year of GH therapy. The aim of this study was to confirm these short-term results and to evaluate the effect of long-term GH therapy on the BMD of children with ISS. PATIENTS AND DESIGN: We treated a group of 16 short, slow-growing but otherwise healthy non-GH-deficient prepubertal children (8 girls and 8 boys) with a chronological age of 9.5 +/- 0.9 years, a bone age of 8.1 +/- 1.2 years and a height of 124.3 +/- 6.3 cm (height-SDS of -2.1 +/- 0.6) with GH at a dose of 0.1 IU/kg/day for 3 consecutive years. MEASUREMENTS: Height was determined at 3-month intervals and annual growth velocities were calculated. Bone ages and BMD were measured every 12 months by dual-energy X-ray absorptiometry, as were serum concentrations of the carboxy-terminal propeptide of type 1 collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type 1 collagen (ICPT). RESULTS: Growth velocity increased from 4.0 +/- 0.8 cm/year to 8.7 +/- 1.5 and 8.0 +/- 1.7 cm/year at 12 and 36 months of GH therapy, respectively, while height-SDS improved from -2.1 +/- 0.6 to -1.6 +/- 0.4 after 36 months of GH (P < 0.0001). Baseline lumbar spine BMD was decreased when compared to that of a control group of healthy children paired for gender, bone age and height (0.640 +/- 0.08 g/cm2vs. 0.730 +/- 0.08 g/cm2; P < 0.003). Lumbar spine BMD increased after 1 year of GH from 0.640 +/- 0.08 to 0.749 +/- 0.08 g/cm2 (P < 0.05), reaching levels similar to that of controls followed for 1 year without therapy (0.749 +/- 0.04 g/cm2vs. 0.760 +/- 0.08 g/cm2). During this period lumbar spine BMD increased 14.5% in the ISS subjects and 3.9% in the controls. Over the following 2 years of GH therapy the lumbar spine BMD of our ISS patients increased at a rate similar to that of the control population, so that after 3 years of consecutive GH therapy the lumbar spine BMD of ISS children was comparable to that of the controls (0.784 +/- 0.12 g/cm2vs. 0.785 +/- 0.09 g/cm2). Femoral neck BMD of our patients was similar to that of the controls at baseline and at 36 months. Following 1 year of GH treatment serum concentrations of PICP increased from 229.6 +/- 63.5 to 358.6 +/- 87.9 micro g/l, while levels of ICTP increased from 9.6 +/- 5.9 to 13.7 +/- 2.1 micro g/l. After 36 months of GH therapy, PICP and ICTP values had decreased to 303.3 +/- 67.2 micro g/l and 11.3 +/- 3.3 micro g/l, respectively, and were no longer significantly different from baseline. CONCLUSIONS: Children with ISS have decreased lumbar spine BMD, which normalized after 1 year of GH. Over the next 2 years of therapy lumbar spine BMD increased at a normal rate, so that after 3 consecutive years of GH the lumbar spine BMD of children with ISS was similar to that of controls. Bone turnover increased with treatment as indicated by a rise in bone formation and bone resorption markers.     

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.     

Effects of alendronate and hormone replacement therapy, alone and in combination, on bone mass and markers of bone turnover in elderly women with osteoporosis

The aim of the study was to compare alendronate, hormone replacement therapy (HRT), and their combination in treatment of osteoporosis in elderly postmenopausal women. Ninety patients, aged 65-80 yr (mean 71), with a T-score of bone mineral density (BMD) of 2.5 or less at either the lumbar spine or the femoral neck were randomized to receive daily 10 mg alendronate (n = 30), 2 mg estradiol plus 1 mg norethisterone acetate (n = 30) (HRT), or their combination (n = 30) for 2 yr. BMD of the lumbar spine and the upper femur was measured at baseline and after 1 and 2 yr of treatment. Urinary excretion of type I collagen aminoterminal telopeptide as related to creatinine and serum type I procollagen aminoterminal propeptide was assayed at baseline and at 6-month intervals thereafter. Increases of 9.1-11.2% in lumbar spine BMD at 2 yr were similar in the study groups. Only HRT increased femoral neck BMD statistically significantly (P < 0.0001 for a change from baseline) at both 1 (+4.9%; P =NS vs. the other groups) and 2 yr (+5.8%; P < 0.05 vs. the other groups). Total hip BMD increased similarly in all study groups. Percentage reductions in urinary type I collagen aminoterminal telopeptide in the HRT group (60.2-62.7%) were significantly smaller than those in the combination group (78.1-80.4%) (P < 0.0001-0.0069) and the alendronate-only group (72.4-76.1%) (P = 0.047 at 24 months). Serum type I procollagen aminoterminal propeptide decreased less in the HRT group (53.6-59.8%) than in the other groups [73.0-75.0% in the alendronate group (P < 0.001 at 12 months); 67.0-71.5% in the combination group (P < 0.0001 at 12 months, P = 0.013 at 24 months)]. We conclude that in elderly postmenopausal women with osteoporosis, the combination of HRT and alendronate did not offer an extra gain of bone mass over either treatment alone. In terms of BMD changes, the single treatments were equally effective, but the reductions in bone markers were less with HRT than with alendronate.     

Long-term skeletal effects of recombinant human growth hormone (rhGH) alone and rhGH combined with alendronate in GH-deficient adults: a seven-year follow-up study

BACKGROUND: GH-deficient patients respond to recombinant human GH (rhGH) replacement therapy by increasing bone mineral density (BMD) at a rate of about 1% a year for at least 4 years. Predictive factors for a beneficial effect on bone are a low bone mass at baseline and gender. Whether the beneficial skeletal effects of GH are sustained in the long term remains to be established. It is also not known whether osteoporotic GH-deficient patients may require additional antiresorptive drugs and whether this treatment would be effective concomitantly with GH replacement. DESIGN: We performed a long-term, controlled study in 30 GH-deficient adults: 15 with osteoporosis and 15 control subjects with low bone mass. All patients were treated with rhGH for at least 4 years; thereafter, 3 years of additional alendronate treatment was given to patients with osteoporosis, while controls continued on GH therapy alone. The GH dose was individualized to maintain an IGF-I within the normal reference range for the duration of the study, and was equal between genders. RESULTS: At the end of 4 years of rhGH replacement therapy, a significant increase in mean lumbar spine BMD was observed in both the osteoporosis group (3.6%) and the control group (7.0%), with no significant difference between groups. Males had a larger increase in BMD than females (P = 0.032). After 4 or 5 years of GH treatment patients with persisting osteoporosis received additional alendronate (10 mg/day) for 3 years. Lumbar spine BMD increased by 8.7% after 3 years (P = 0.001) vs 1.5% (P = NS) in the control group continuing on rhGH replacement alone. The alendronate effect was gender independent (P = 0.59). Mean bone area of the lumbar spine did not change in both groups for the duration of the study. Femoral neck BMD increased significantly in the osteoporosis group (3.5%) and was unchanged in the control group. Five osteoporotic GH-deficient patients had a total of 12 vertebral fractures before start of alendronate. Only one of these patients developed two new vertebral fractures within the first year of treatment with alendronate. CONCLUSION: We observed a significant increase in lumbar spine BMD in the first 4 years of rhGH replacement. The effect of GH on bone was gender dependent, but not BMD dependent. After more than 4 years of GH replacement, BMD seemed to reach a plateau, at least as measured in the 3-4 years thereafter, as no significant increase was present in patients treated with GH alone. By contrast, alendronate rapidly augmented BMD and this effect was maintained for at least 3 years. These increases in BMD were associated with a low incidence of (vertebral) fractures. The long-term use of GH does not preclude a beneficial effect of an additional antiresorptive agent in GH-deficient patients with osteoporosis.     

Pattern of bone mineral density in idiopathic male osteoporosis

The mechanisms of male idiopathic osteoporosis are little known. We evaluated bone mineral loss by dual-energy X-ray absorptiometry and determined its cortical or trabecular nature in a cohort of men with idiopathic osteoporosis with fractures. Thirty-nine men (mean age 60?±?13?years), with negative investigations for the cause of osteoporosis, were studied. All had fragility fractures: vertebral 51%, peripheral 25%, and both types 24%. Bone density was measured at the lumbar spine (L2-L4), total hip and whole body. The limb/axial skeleton (spine?+?hips) and hip/L2-L4 BMD ratios were calculated. Serum 25-hydroxy-vitamin D, PTH, bone alkaline phosphatase and CTX were measured. Bone mineral loss predominated at the lumbar spine (mean L2-L4 T-score -3?±?0.93, mean total hip T-score -1.87?±?0.75). Limb/axial skeleton and total hip/L2-L4 BMD were strongly correlated, but not hip and spine BMD. The ratio values were widely scattered, indicating markedly heterogeneous bone loss. Vitamin D, PTH, bone alkaline phosphatase and CTX levels did not differ between predominantly trabecular and cortical osteoporosis. Bone mineral density measurement in male idiopathic osteoporosis with fractures demonstrated that bone loss predominated in the spine and that it was very heterogeneous, principally affecting cortical or trabecular bone depending on the patient.     

The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race

CONTEXT: Low bone mass may increase risk of fracture. Several chronic medical conditions, medications, and lifestyle factors affect bone mineral accrual. Appropriate reference values are essential for identification of children with bone deficits. OBJECTIVE: Our objective was to establish reference curves for bone mineral content (BMC) and density (BMD) in children. DESIGN AND SETTING: The Bone Mineral Density in Childhood Study is an ongoing longitudinal study in which measurements are obtained annually at five clinical centers in the United States. PARTICIPANTS: Participants included 1554 healthy children (761 male, 793 female), ages 6-16 yr, of all ethnicities. MAIN OUTCOME MEASURES: Scans of the whole body, lumbar spine, hip, and forearm were obtained using dual-energy x-ray absorptiometry. Percentile curves based on three annual measurements were generated using the LMS statistical procedure. RESULTS: BMC of the whole body and lumbar spine and BMD of the whole body, lumbar spine, total hip, femoral neck, and forearm are given for specific percentiles by sex, age, and race (Black vs. non-Black). BMC and BMD were higher for Blacks at all skeletal sites (P < 0.0001). BMC and BMD increased with age, and a plateau was not evident by age 16 (girls) or age 17 (boys). The variation in BMC and BMD also increased with age. CONCLUSIONS: Age-, race-, and sex-specific reference curves can be used to help identify children with bone deficits and for monitoring changes in bone in response to chronic diseases or therapies.     

Treatment of post-menopausal osteoporosis with a combination of growth hormone and pamidronate: a placebo controlled trial

OBJECTIVE It is known that growth hormone can Induce accelerated bone turnover in GH deficient people as well as healthy elderly people. In this study we examined the effect of recombinant human GH (rhGH) on bone mineral mass and bone turnover in the presence of the bone resorption inhibiting agent, pamidronate. Effects on body composition were also studied. METHODS Twenty-one post-menopausal osteoporotic women were treated with the bisphosphonate pamidronate during 12 months. During the Initial 6 months rhGH (0.0675 IU/kg, 3 times/week) was administered In a placebo controlled fashion (10 vs 11 patients). MEASUREMENTS Bone mineral Content (BMC) of the lumbar spine and femoral neck was measured with dual-energy X-ray absorptiometry and BMC of the distal and proximal forearm with single-photon absorptiometry. Body composition was measured with bioelectrical Impedance and total body dual-energy X-ray absorptiometry. Serum IGF-I and biochemical indices of bone turnover were also measured. RESULTS The group treated with rhGH showed a two to three-fold Increase In serum IGF-I levels. No effects on bone mineral mass were observed in the group treated with rhGH, either after the Initial 6 months of treatment with rhGH or after the total period of 12 months. In women treated with pamidronate, however, a consistent increase of about 5% at the lumbar spine and somewhat less in the distal forearm was reached from 6 months onwards. In neither group was any change observed in BMC at the femoral neck or forearm. Compared to baseline, the biochemical measurements of bone turnover showed a decrease of about 50% in the pamidronate treated group, but this effect was blunted in the group additionally treated with rhGH. The body composition measurements showed clear effects of rhGH administration: a decrease in fat mass of about 5% and an increase In lean body mass of about 3%. However, these effects disappeared after the treatment with rhGH was stopped and both fat mass and lean body mass returned to Initial values. CONCLUSIONS The present study suggests that treatment with rhGH blunted both the pamidronate induced accumulation of bone mineral mass and the reduction of biochemical markers of bone turnover. Furthermore, the positive effect of rhGH on body composition disappears completely after cessation of treatment with rhGH.     

Effects of neridronate treatment in elderly women with osteoporosis

Osteoporosis is a common disorder, especially among elderly post-menopausal women. Elderly women are often affected by co-morbidities, impaired gastrointestinal function and reduced mobility; therefore, the treatment strategy for their osteoporosis can be difficult. In this randomized pilot study, we have investigated the effects of a 12-month treatment with neridronate on bone mineral density (BMD), bone turnover markers and quality of life (QoL). The study included 40 women (age, 65-80 yr; post-menopausal period, >15yr) from a single osteoporosis centre. Twenty women received a monthly im injection of 25 mg of neridronate associated with a daily dose of 500 mg of calcium and 400 U of vitamin D. Twenty women received calcium plus vitamin D supplements alone. Changes in BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Serum type I collagen C-telopeptide (sCTX), urinary free-deoxypyridinoline (ufDPD), bone alkaline phosphatase (ALP) and serum osteocalcin levels were determined. For the QoL assessment, the Italian version of the SF-36 test was administrated. Spine and hip BMD rose by 6.6 +/- 3 and 4.2 +/- 2.3%, respectively (p < 0.05), after 12 months of neridronate treatment. Markers of skeletal turnover significantly fell already after 3 months of neridronate treatment and decreased progressively thereafter within 12 months. The mean decrease at 12 months ranged from 38 +/- 11% for sCTX to 25.2 +/- 15% for ufDPD (p < 0.001, all). The mean improvement in QoL in the treated group was 45.7% for bodily pain, 37.5% for general health perception, 23.1% for vitality, 18% for emotional role functioning and 12% for physical role functioning. The changes observed in BMD, turnover markers and QoL in the untreated group were ns. The intermittent neridronate administration was easily manageable and well tolerated. In conclusion, neridronate currently represents a valid option for the treatment of osteoporosis, since it helps just as much as oral BPs in the improvement of BMD and in particular conditions it can be even more effective.     

Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate

Treatment of osteoporosis with PTH causes a marked increase in vertebral bone mineral density (BMD). However, this effect is rapidly reversed when the treatment is stopped. The purpose of the present study was to determine whether the bisphosphonate alendronate could preserve or enhance bone density in patients previously treated with PTH. Sixty-six postmenopausal osteoporotic women were treated for 1 yr with 50, 75, or 100 microg recombinant human PTH-(1-84) or placebo, and then were given 10 mg alendronate daily for an additional year. BMD was measured in the femoral neck, lumbar spine, and whole body. Markers of bone turnover included skeletal alkaline phosphatase, osteocalcin, and N-telopeptide. During the first year, changes in BMD (mean +/- SD) in women receiving PTH (all doses combined) were 7.1 +/- 5.6% (spine), 0.3 +/- 6.2% (femoral neck), and -2.3 +/- 3.3% (total body). After switching to alendronate for 1 yr in women who previously had received PTH, mean changes in BMD were 13.4 +/- 6.4% (spine), 4.4 +/- 7.2% (femoral neck), and 2.6 +/- 3.1% (whole body). In the subgroup of patients who had received the highest dose of PTH, the mean increase in vertebral BMD was 14.6 +/- 7.9%. All markers of bone turnover increased during treatment with PTH and decreased to below baseline after 1 yr of alendronate. In conclusion, sequential treatment of osteoporosis with PTH and alendronate results in an increase in vertebral bone density that is considerably more than has been reported with alendronate or estrogens alone. This combination of drugs may be a useful approach to maximizing bone density in women with vertebral osteoporosis.     

Bone mineral content and bone mineral density at lumbar spine and forearm in Chinese girls aged 6-18 years

We investigated the age-related bone mineral content (BMC), bone mineral density (BMD) and the tempo of growth in BMC and BMD at lumbar spine and forearm in 455 Chinese girls aged 6-18 yr. BMC and BMD at the anteroposterior lumbar spine (LS), the left forearm (radius+ulna ultradistal, R+UUD) and one-third region (R+U1/3) were measured using a dual-energy X-ray bone densitometer (DXA). BMC and BMD exhibited different change patterns with the age changes. There were significant correlations between age, height, weight and BMC and BMD at LS, R+UUD and R+U1/3 sites. BMC and BMD increased significantly with increments in pubertal stages at LS, R+UUD and R+U1/3 sites. In conclusion, our study showed that Tanner stage had a significant positive association with BMC and BMD of the lumbar spine and forearm. The differences were found in the growth tempo of BMC and BMD within a region and between the spine and forearm. Both BMD and BMC were recommended to evaluate the bone health in children and adolescents.     

Effects of alendronate on metacarpal and lumbar bone mineral density,bone resorption,and chronic back pain in postmenopausal women with osteoporosis

The purpose of this study was to investigate the effect of alendronate on metacarpal and lumbar bone mineral density (BMD), bone resorption, and chronic back pain in postmenopausal women with osteoporosis. Eighty postmenopausal women with osteoporosis, 59–88 years of age, were divided into two groups of 40 each according to the site of BMD measurement: the metacarpus (M) and the lumbar spine (L). All of them were treated with alendronate (5 mg/day) for 12 months. Metacarpal or lumbar BMD was measured by computed X-ray densitometry or dual-energy X-ray absorptiometry in the M or the L group, respectively, at baseline and every 6 months. Urinary cross-linked N-terminal telopeptides of type I collagen (NTX) were measured by enzyme-linked immunosorbent assay, and chronic back pain was evaluated by face scale score at baseline and every 6 months in both groups. There were no significant differences in baseline characteristics, including age, body mass index, years since menopause, urinary NTX level, face scale score, or number of prevalent vertebral fractures per patient between the two groups. Urinary NTX level was reduced and chronic back pain was improved similarly in both groups. Whereas metacarpal BMD did not significantly change in the M group (0.20% increase), lumbar BMD increased by 8.15% in the L group. These results suggest that although alendronate increases BMD of the lumbar spine, which is rich in cancellous bone, and improves chronic back pain, with suppression of bone resorption in postmenopausal women with osteoporosis, it may fail to increase cortical BMD of the metacarpus, a distal site of the upper extremity.Abbreviations ALP Alkaline phosphatase - BMD Bone mineral density - DXA Dual-energy X-ray absorptiometry - NTX Cross-linked N-terminal telopeptides of type I collagen