Changes of bone mineral density, quantitative ultrasound parameters and markers of bone turnover during treatment of hyperthyroidism.

BACKGROUND: The extent of reversibility of loss of bone mass density (BMD) in hyperthyroid patients after treatment is not clear. METHODS: The bone density measured by dual X-ray absorptiometry (DXA), the parameters of quantitative ultrasound (QUS) and biochemical markers of bone turnover of 22 patients were measured before and after one year of treatment with thiamazole and levothyroxine. RESULTS: The mean BMD of lumbar spine, femoral neck, Ward triangle and total hip bone density increased by 5.9, 3.8, 3.0 and 6.7%, respectively, after one year of treatment, all significant increases except the increase in Ward triangle bone mass density. There was no significant change in QUS parameters, although the increase in broadband ultrasound attenuation (BUA) of the left and right calcaneus of 5.2 and 4.2%, respectively, suggests reversibility in the long term. Urinary pyridinoline cross-links declined significantly and normalised after treatment. Bone-specific alkaline phosphatase declined after an initial rise, not (yet) reaching normal values after one year of treatment. CONCLUSION: The decline in BMD in hyperthyroid patients measured by DXA seems to be reversible after treatment of hyperthyroidism, whereas a change in the QUS parameters, probably also an indicator of bone elasticity and architecture, could not be found.

Administration of a single low dose of recombinant human thyrotropin significantly enhances thyroid radioiodide uptake in nontoxic nodular goiter.

Radioiodine (131I) is increasingly used as treatment for volume reduction of nontoxic, nodular goiter. A high dose of 131I is often needed because of low thyroid radioiodide uptake (RAIU). We investigated whether pretreatment with a single, low dose of recombinant human TSH (rhTSH; Thyrogen, Genzyme Transgenics Corp.) enhances RAIU in 15 patients with nontoxic, nodular goiter (14 women and 1 man; aged 61+/-11 yr). Four patients were studied twice, and 1 patient was studied 3 times. RAIU was measured both under basal conditions and after pretreatment (im) with rhTSH, given either 2 h (0.01 mg; n = 7) or 24 h [0.01 mg (n = 7) or 0.03 mg (n = 7)] before 131I administration (20-40 microCi). Serum levels of TSH, free T4 (FT4), and total T3 were measured at 2, 5, 8, 24, 48, 72, 96, and 192 h after rhTSH administration. After administration of 0.01 mg rhTSH, serum TSH rose from 0.7+/-0.5 to a peaklevel of 4.4+/-1.1 mU/L (P < 0.0001), FT4 rose from 16.0+/-2.6 to 18.5+/-3.7 pmol/L (P < 0.0001), and T3 rose from 2.10+/-0.41 to 2.63 - 0.66 nmol/L (P < 0.0001). After administration of 0.03 mg rhTSH, TSH rose from 0.6+/-0.4 to 15.8+/-2.3 mU/L (P < 0.0001), FT4 rose from 15.2+/-1.5 to 21.7+/-2.9 pmol/L (P < 0.0001), and T3 rose from 1.90+/-0.43 to 3.19+/-0.61 nmol/L (P < 0.0001). Peak TSH levels were reached at 5-8 h and peak FT4 and T3 levels at 8-96 h after rhTSH administration. Administration of 0.01 mg rhTSH 2 h before 131I increased 24-h RAIU from 30+/-11% to 42+/-10% (P < 0.02), 0.01 mg rhTSH administered 24 h before 131I increased 24-h RAIU from 29+/-10% to 51+/-10% (P < 0.0001), and 0.03 mg rhTSH administered 24 h before 131I increased 24-h RAIU from 33+/-11% to 63+/-9% (P < 0.0001). After administration of 0.01 mg rhTSH 2 h before 131I, 24-h RAIU did not increase in 1 patient, whereas the increase in 24-h RAIU was less than 10% in 2 other patients. In contrast, administration of rhTSH 24 h before 131I increased 24-h RAIU by more than 10% in all 14 patients (by >20% in 10 and by >30% in 6). In conclusion, pretreatment with a single, low dose of rhTSH in patients with nontoxic, nodular goiter increased RAIU considerably. Our observations hold promise that administration of rhTSH before 131I therapy for nontoxic, nodular goiter will allow treatment with lower doses of 131I in these patients.

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.

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 patients 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, while after 2 weeks 150 mg pamidronate per day was added. RESULTS: In the first study period (GH only) there was a significant increase of phosphate reabsorption, without a change in serum PTH and 1.25-(OH)2D3 levels. This suggests a specific effect of GH or IGF-I on renal phosphate handling. This was supported by the close correlation between serum IGF-I levels and TmP/GFR (r = 0.75, P < 0.0001). When GH was administered together with pamidronate, this correlation was less, but remained significant (r = 0.44, P < 0.001). 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 administration of the combination of GH and pamidronate (measured with dual-energy X-ray absorptiometry). 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 reabsorption. Furthermore, it reduces GH induced bone turnover and prevents the initial decrease in bone mineral content seen during GH treatment alone, resulting in a beneficial effect on bone mineral 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 stimulation of bone turnover.

Bone mineral density in healthy Dutch women: spine and hip measurements using dual-energy X-ray absorptiometry.

OBJECTIVE: To investigate in healthy normal Dutch women the age-associated changes in bone mineral density (BMD) and the effect on bone mass of the menopause and potential risk factors. METHODS: In 260 healthy Dutch women BMD was measured in the lumbar spine and three regions of the proximal femur (Ward's triangle, femoral neck and trochanter), using dual energy X-ray absorptiometry (DXA). The subjects were interviewed using a structured questionnaire on age, reproductive history and gynaecological status, height, weight and consumption of tobacco and alcohol. RESULTS: In 125 premenopausal women a small age-related bone loss was observed at both the lumbar spine and proximal femur, while in postmenopausal women (n = 135) a 2-3 times higher age-related loss was observed. Expressed in years since the menopause this postmenopausal loss was found to be exponential (p < 0.001). After adjustment for age there appears to be a relationship between actual age of menopause and BMD at the lumbar spine and femoral neck. After adjustment for age and actual age of menopause we observed a small negative effect of breastfeeding, whereas parity, current alcohol use and smoking showed no additional effect on BMD in this cohort. For all women (n = 260) a highly significant correlation between BMD and body mass index was found. CONCLUSIONS: In healthy Dutch women we observed a small premenopausal and an accelerated postmenopausal bone loss in both the lumbar spine and proximal femur. Except for breastfeeding, no other risk factors could be identified.

Course of bone mass during and after hormonal replacement therapy with and without addition of nandrolone decanoate.

A total of 33 women with postmenopausal osteoporosis were matched pairwise by age, years since menopause, and body mass index and randomized to receive either cyclic estrogen-progestagen replacement treatment (group 1) or the same treatment plus nandrolone decanoate (ND; group 2). Both groups were treated during 3 years and subsequently followed for another year off treatment. A year after cessation of the treatment the distal forearm bone mineral content in group 2 was significantly higher than that in group 1. Bone mass measurements in the axial skeleton already showed a significant difference in favor of group 2 after 3 years treatment, which persisted during the year off treatment. The decline in lumbar bone mineral mass and density in the 1 year off treatment was similar in both groups. Correction for body mass did not change these results. Bone turnover parameters did not show significant differences between the two groups after cessation of treatment. A higher muscle mass, induced by ND, could partly explain the differences between the groups since even 1 year after treatment was stopped an increased serum creatinine level was still observed in group 2.

Can nandrolone add to the effect of hormonal replacement therapy in postmenopausal osteoporosis?

Thirty-six women with postmenopausal osteoporosis (31 of them with at least one non-traumatic vertebral compression fracture) were matched pair-wise as to age, years since menopause and body mass index and randomized to receive either cyclical estrogen-progestagen replacement treatment (group 1) or the same treatment plus nandrolone decanoate (group 2). During the first year of treatment in both groups the forearm BMC (SPA) rose proximally and distally 2-3%. Over 2 years the increments of forearm BMC in both groups were up to 4.5%. Lumbar BMC (DPA) rose in both groups nearly 10% over the first year and 12-12.5% over 2 years. The cancellous bone density of L3 (QCT) showed in 6 months an increase of 21% in group 1 and 29% in group 2 to subsequently stay at that level. All these changes from the basal levels were highly significant but there were no significant differences between the two groups. These two conclusions were also drawn with regard to the induced fall of serum alkaline phosphatase (-23%), osteocalcin (-35% to -44%) and procollagen I (-15% to -22%) and of the fasting urinary hydroxyproline (-33% to -36%). No significant increase in the number of newly deformed vertebrae occurred in 2 years.