[Hypercalcemic crisis and hypocalcemic tetany]. / Hyperkalzämische Krise und hypokalzämische Tetanie.

A serum calcium level >3.5 mmol/l together with clinical symptoms such as muscle weakness, fatigue, nausea, vomiting, pancreatitis or even coma are characteristic for a hypercalcemic crisis (HC). Primary hyperparathyroidism (1HPT) and malignancy-associated hypercalcemia are the most frequent causal diseases for a HC. The analysis of serum levels for calcium, phosphorous, intact parathyroid hormone, electrophoresis and renal function parameters indicate which further radiological, scintigraphic or serum diagnostic steps are adequate to identify the cause of the patient's acute situation (i. e. most frequently 1HPT or malignant disease with bone involvement, e. g. myeloma) and thus to initiate the required surgical or oncological intervention. However, the primary goals in the treatment of HC include correcting dehydration and improving kidney function, lowering calcium levels and decreasing osteoclastic bone resorption. The goals are accomplished by volume repletion, forced diuresis, antiresorptive agents and hemodialysis on an intensive care unit. Hypocalcemic tetany (HT) is the consequence of severely lowered calcium levels (<2.0 mmol/l), usually in patients with chronic hypocalcemia. The causal disease for hypocalcemic tetany is frequently a lack of parathyroid hormone (PTH), (e. g. as a complication of thyroid surgery) or, rarely, resistance to PTH. HT due to severe and painful clinical symptoms requires rapid i. v. calcium replacement by central venous catheter on an intensive care unit. For the treatment of chronic hypocalcemia oral calcium and 25OH-vitamin D or even 1,25(OH)2-vitamin D3 and magnesium supplements may be necessary to achieve the desired low normal calcium levels. Thiazides are useful to reduce renal calcium loss and to stabilize the calcium levels. Some patients continue to exhibit clinical symptoms despite adequate calcium levels; in these cases s. c. parathyroid hormone 1-84 should be considered to stabilize calcium levels and to lower the dosage of calcium and vitamin D supplements.

[Prevention of aortic erosion by a bone cement skid : Thoracic endovascular aortic repair following kyphoplasty]. / Pelottierung der A. thoracica descendens durch einen Zementsporn : Endovaskuläre Behandlung nach Kyphoplastie.

The underlying case report describes the successful endovascular prevention of an aortic injury by a bone cement skid after kyphoplasty. The intervention was performed in order to prohibit fatal aortic rupture or embolisation and underlines the role of vascular surgery techniques in interdisciplinary clinical networks.

[Kyphoplasty-Vertebroplasty. A critical assessment]. / Kyphoplastie-Vertebroplastie. Eine kritische Standortbestimmung.

CLINICAL ISSUE: Painful vertebral compression fractures. STANDARD TREATMENT: Analgesia. TREATMENT INNOVATIONS: Osteoplastic procedures, such as kyphoplasty and vertebroplasty. DIAGNOSTIC WORKUP: Anamnestic and radiological associations of clinical complaints with the radiomorphological findings of vertebral compression fractures are required for an adequate consideration to assess whether an osteoplastic procedure should be carried out. A computed tomography (CT) scan allows a reliable judgement whether an osteoplastic procedure is technically feasible and promising to improve the local vertebral fracture-associated pain. PERFORMANCE: Prospective controlled trials have demonstrated a satisfactory improvement of back pain associated with vertebral fractures and parameters of quality of life by osteoplastic interventions. ACHIEVEMENTS: No prospective, truly sham-controlled blind trials are currently available which demonstrate an advantage of osteoplastic interventions compared to standard pain treatment; however, the currently published prospective controlled trials show a satisfactory pain reduction by osteoplastic interventions, such as kyphoplasty and vertebroplasty. PRACTICAL RECOMMENDATIONS: Painful vertebral fractures and progressive loss of vertebral height of compression fractures should be evaluated in an interdisciplinary team consisting of radiologists, spinal surgeons and internists to assess whether an osteoplastic procedure is technically feasible and promising to improve local pain and immobility associated with vertebral fractures.

The effect of zoledronic acid on the fracture risk in men with osteoporosis.

BACKGROUND: Prospective, placebo-controlled, double-blind, randomized studies on osteoporosis treatment with bisphosphonates in men are rare. This review focuses on a recent trial and compares the results with other studies. METHODS: This review provides a summary of recent literature on fracture risk in men following treatment with zoledronic acid. According to a recent clinical study with 1,199 men, zoledronic acid was linked to a lower risk of vertebral fractures. In this manuscript, a re-analysis of the presented statistical data will be demonstrated by performing a Bonferroni-correction to adjust for type 1 error accumulation in multiple statistical tests. RESULTS: It will be shown that the provided evidence linking zoledronic acid to a lower fracture risk in male osteoporosis is true, but less pronounced than originally assumed. CONCLUSION: Comparative clinical studies are recommended, where the benefits of different bisphosphonates are compared to each other under the same experimental conditions.

[Disorders of calcium metabolism]. / Störungen des Kalziumstoffwechsels.

The majority of clinical complaints derive from disorders of calcium metabolism and are associated with a wide variety of clinical symptoms caused by numerous diseases with entirely different types of pathophysiology. The prognosis varies from favorable to fatal depending on the pathophysiology of the underlying disorder of calcium metabolism; therefore, the diagnostic work-up aims to quickly identify the underlying disease causing the disturbance in calcium homeostasis. Every clinical situation with a diminished state of calcium absorption is treated with calcium and vitamin D in varying doses whereas every disorder with an increased calcium absorptive or resorptive state is treated with improved diuresis in addition to antiresorptive drugs, such as bisphosphonates. In many situations the management of a disturbed calcium balance requires an interdisciplinary approach in order to treat the underlying disease in parallel with correction of the calcium homeostasis.

Dynamic contrast-enhanced MRI for monitoring bisphosphonate therapy in Paget's disease of bone.

PURPOSE: The purpose of this study was to evaluate changes in regional bone perfusion in Paget's disease (PD) following bisphosphonate therapy. We used dynamic contrast-enhanced MRI (DCE-MRI) for assessment of bone perfusion and compared MRI findings with alkaline phosphatase (AP) as a serum marker of bone turnover. MATERIALS AND METHODS: We examined 20 patients (8 women, 12 men, 66 ± 11 years) with symptomatic PD of the axial skeleton. Patients were selected for infusion therapy with the bisphosphonate pamidronate. The most affected bone of lumbar spine or pelvis was examined by DCE-MRI prior to therapy and after a 6-month follow-up. The contrast uptake was evaluated using a two-compartment model with the parameters amplitude A and exchange rate constant K(ep). Color-coded parametric images were generated to visualize bone vascularization. RESULTS: After a 6-month follow-up there was a significant decrease in alkaline phosphatase and in DCE-MRI parameters A and K(ep) (p < 0.0001). Patients without previous bisphosphonate treatment showed a significantly greater decrease in alkaline phosphatase and K(ep) (p < 0.001). CONCLUSION: DCE-MRI shows a significant reduction in regional bone perfusion in PD following parenteral bisphosphonate treatment. Reduction in bone perfusion is greater in bisphosphonate-naïve patients than in those who had been previously treated.

[Role and limitations of vertebroplasty and kyphoplasty in the management of spinal metastases]. / Rolle und Grenzen der Vertebro-/Kyphoplastie im Metastasenmanagement der Wirbelsäule.

The spine is the most common site for skeletal metastases. Tumor-induced osteolysis may lead to pain, dysfunction and ultimately vertebral fracture. In some patients conventional surgery is not suitable because of the palliative therapy approach. Just for this patient population it was shown that cement augmentation of the vertebra is an effective therapy option and plays an important role. Nevertheless, cement augmentation of the vertebra has its limitations and should only be applied by appropriate indications.

Glucocorticoids regulate the expression of the human osteoblastic endothelin A receptor gene.

The endothelial cell-derived peptide endothelin 1 (ET1) stimulates cell proliferation and differentiated functions of human osteoblastic cells (HOC), and HOC constitutively express the endothelin A receptor (ETRA). Therefore, ET1 may play an important role in the regulation of bone cell metabolism. As glucocorticoids (GC) exert a profound influence on bone metabolism and increase the effects of ET1 on bone cell metabolism in vitro, the effects of GC on ETRA expression in HOC were investigated. Dexamethasone (DEX) increased ETRA mRNA levels in a dose- and time-dependent fashion. The effects of dexamethasone, prednisolone, and deflazacort on the increase of ETRA mRNA levels correlate positively with their binding affinity to the GC receptor. Scatchard analysis of ET1 binding data to HOC revealed that DEX increased the binding capacity for ET1 from 25,300 to 62,800 binding sites per osteoblastic cell, leading to an enhanced mitogenic effect of ET1 on HOC after preincubation with DEX. Transiently transfected primary HOC with a reporter gene construct, containing the 5'-flanking region of the ETRA gene fused to luciferase gene, showed a promoter-dependent expression of the reporter gene and the induction of reporter gene expression by DEX treatment. Total RNA extracts of femoral head biopsies with osteonecrotic lesions from GC-treated patients showed threefold higher ETRA mRNA levels compared with extracts of bone biopsies from patients with traumatically induced osteonecrosis and coxarthrosis. Furthermore, GC treatment increased plasma ET1 levels by 50% compared with pretreatment values. These findings suggest that GC induced upregulation of ETRA, and ET1 plasma levels enhance ET1's anabolic action on bone cell metabolism. Increased ET1 concentrations may also impair bone perfusion by vasoconstriction in a metabolically activated skeletal region.

[Screening for osteoporosis]. / Osteoporosescreening.

Osteoporosis affects approximately 7 million patients in Germany and severely impairs quality of life. The clinical picture, subjective complaints as well as the presence or absence of risk factors are essential to determine the individual risk profile and to decide on possible serum blood tests, osteodensitometry, and X-ray examinations. Back pain or other clinical evidence of impaired bone stability should be evaluated with X-ray studies of the spine. If osteoporosis and an increased risk of fracture are present, treatment is indicated which includes an evidence-based pharmaceutical regimen in order to increase bone stability and to lower the risk of fractures. Drug treatment with adequate calcium and vitamin D supplementation and antiresorptive or osteoanabolic substances, usually for 3-5 years, should be accompanied by pain medication and neuromuscular rehabilitation to help prevent falls and maintain independence of the elderly.

[Kyphoplasty : method for minimally invasive treatment of painful vertebral fractures]. / Kyphoplastie : Minimal-invasives Verfahren zur Versorgung schmerzhafter Wirbelkörperfrakturen.

Painful osteoporotic and malignant vertebral fractures are frequent causes of chronic back pain with negative consequences regarding immobility, quality of life, morbidity, mortality, and fracture incidence. The best currently available evidence-based treatment reduces vertebral fracture risk but does not totally prevent follow-up fractures. Kyphoplasty is a causal treatment of pain by internal stabilization that prevents the ongoing pain of constant vertebral (micro-)fracture. The indication for this minimally invasive procedure requires interdisciplinary discussion of the individual case to guarantee technical feasibility, increase the likelihood that kyphoplasty will indeed reduce pain, and embed this procedure in the individual patient's long-term therapeutic concept or treatment of painful vertebral metastases. In addition to internal stabilization of painful vertebral fractures, kyphoplasty seeks to restore lost vertebral height, which appears promising in acute and painful vertebral fractures. Available controlled prospective studies demonstrate long-term patient benefits in terms of pain reduction, mobility, and improved quality of life.

Long-term treatment of central Cushing's syndrome with rosiglitazone.

CONTEXT: Central Cushing's syndrome is not always curable by surgery or radiation of the pituitary. Medical treatment is often not possible or effective. Some studies revealed beneficial effects of the PPARgamma (Peroxisome-Proliferator-Activator- Receptor-gamma)-agonist rosiglitazone (RG) in in vitro studies, animal models and short term clinical studies. OBJECTIVE: of this study was to observe the long-term effects of RG-treatment on cortisol- and ACTH -secretion, clinical outcomes and morphological changes of the pituitary in patients with persistent ACTH-overproduction despite previous operation and radiation. DESIGN, SETTING AND PATIENTS: 14 patients with persistent central ACTH -production were included and monitored over a period up to 12 months. RG was administered daily and increased to a maximum dosage of 24 mg daily, according to the response of ACTH and cortisol secretion. ACTH and cortisol were measured at least every 4 weeks during RG treatment. RESULTS: Patients were treated between 4 and 12 months with RG (mean 6.8 months). Compared to baseline, ACTH- and cortisol levels dropped significantly (p<0.01) after 12, 16, 20, 24 and 28 weeks but thereafter rose again during the study period, despite continuous RG- treatment and dose increase up to the maximum dosage. This was paralleled by reocurrence of clinical symptoms. MRI-scans were performed in 6 patients because of persisting visible adenoma, but showed no morphological changes. CONCLUSION: RG seems not to be a long-term treatment option for patients with persistent central ACTH-evcess. Though, in order to reduce perioperative complications, short term treatment of patients could be an alternative.

Endothelin-1 levels in patients with Paget's disease of bone.

A locally accelerated bone turnover is the pathophysiological basis of Paget's disease of bone (PD) and may result in severe bone deformations and pain. Affected bone sites are hypervascularized. Secreted endothelial products such as endothelin-1 (ET-1), influence bone metabolism. We investigated a possible correlation between ET-1 plasma concentrations and bone metabolism in patients with PD and whether ET-1 plasma levels are regulated by i. v. bisphosphonate treatment. Plasma ET-1 levels were determined in 22 patients with PD and found to be significantly (p = 0.006) elevated (0.75 +/- 0.48 fmol/ml) compared to 19 healthy controls (0.20 +/- 0.24 fmol/ml). In a group of five patients with PD, plasma ET-1 levels were determined before and after treatment with i. v. pamidronate. On the average, ET-1 levels decreased by 21 % after pamidronate infusions (p = 0.045). The results suggest that bone metabolism in pagetic bone affects endothelial cell metabolism and may also be modulated by endothelial cell products. ET-1 plasma levels may indicate PD activity.

[Prevalence of latent and manifest hyperthyroidism in an iodine-deficient area: non-selected patient population admitted for CT studies with iodine-containing contrast agents]. / Prävalenz der latenten und manifesten Hyperthyreose in einem Jodmangelgebiet: Erhebung an einem nichtselektionierten Patientenkollektiv vor Durchführung einer Computertomographie mit jodhaltigem Kontrastmittel.

PURPOSE: To evaluate the prevalence of latent and manifest hyperthyroidism in a non-selected group of patients admitted for contrast enhanced CT studies blood samples were tested for the levels of thyroid-stimulating hormone (TSH). MATERIAL AND METHODS: TSH blood levels were obtained in 548 consecutive patients who were scheduled for contrast-enhanced (Iopromide; 300 mg iodine/ml) CT scanning. In case of TSH levels < 0.4 mU/l, blood samples were also tested for triiodothyronine (T3) and tetraiodothyronine (T4) blood levels, and treatment with Irenat (sodium perchlorate) was commenced before scanning. In case of TSH levels < 0.1 mU/l, CT scanning was not performed but further evaluation of the thyroid function was initiated. RESULTS: TSH blood levels ranged from 0.4 to 7.5 mU/l in 512 patients, and 36 patients (6.6%) had TSH blood levels < 0.4 mU/l and 9 patients blood levels < 0.1 mU/l, with 32 of those patients (5.8%) having regular T3 and T4 blood levels consistent with latent hyperthyroidism. In 4 patients (0.8%), T3 or T4 blood levels were increased consistent with manifest hyperthyroidism. CONCLUSION: In South Germany, the prevalence of latent or manifest hyperthyroidism in a non-selected patient group is high. Therefore TSH blood levels should be obtained prior to contrast-enhanced CT studies.

Gonadal and adrenal androgens are potent regulators of human bone cell metabolism in vitro.

Androgens stimulate bone formation and play an important role in the maintenance of bone mass. Clinical observations suggest that both gonadal and adrenal androgens contribute to the positive impact of androgenic steroids on bone metabolism. We investigated the mechanism of action of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfated compound dehydroepiandrosterone sulfate (DHEAS) on human osteoblastic cells (HOCs) in vitro. The DHEA- and DHEAS-induced effects were analyzed in parallel with the actions elicited by the gonadal androgen dihydrotestosterone (DHT). There was no qualitative difference between the effects of gonadal and adrenal androgens on HOC metabolism in vitro. Both were stimulatory as regards cell proliferation and differentiated functions, but the gonadal androgen DHT was significantly more potent than DHEA. The actions of DHT and DHEA on HOC proliferation and alkaline phosphatase (ALP) production could be prevented by the androgen receptor antagonist hydroxyflutamide and inhibitory transforming growth factor beta antibodies (TGF-beta ab), respectively, but were not affected by the presence of the 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) and 5-alpha-reductase (5-AR) inhibitor 17 beta-N,N-diethylcarbamoyl-4-methyl- 4aza-5 alpha-androstan-3-one (4-MA). This indicates that DHT and DHEA (1) exert their mitogenic effects by androgen receptor-mediated mechanisms, (2) stimulate ALP production by increased TGF-beta expression, (3) that the action of DHT is not affected by the presence of 4-MA, and that (4) DHEA does not need to be metabolized by 3 beta HSD or 5-AR first to exert its effects on HOCs in vitro.

Androgens directly stimulate proliferation of bone cells in vitro.

This report describes the first observation of a direct mitogenic effect of androgens on isolated osteoblastic cells in serum-free culture. [3H]thymidine incorporation into DNA and cell counts were used as measures of cell proliferation. The percentage of cells that stained for alkaline phosphatase was used as a measure of differentiation. Dihydrotestosterone (DHT) enhanced mouse osteoblastic cell proliferation in a dose dependent manner over a wide range of doses (10(-8) to 10(-11) molar), and was maximally active at 10(-9) M. DHT also stimulated proliferation in human osteoblast cell cultures and in cultures of the human osteosarcoma cell line, TE89. Testosterone, fluoxymesterone (a synthetic androgenic steroid) and methenolone (an anabolic steroid) were also mitogenic in the mouse bone cell system. The mitogenic effect of DHT on bone cells was inhibited by antiandrogens (hydroxyflutamide and cyproterone acetate) which compete for binding to the androgen receptor. In addition to effects on cell proliferation, DHT increased the percentage of alkaline phosphatase (ALP) positive cells in all three bone cell systems tested, and this effect was inhibited by antiandrogens. We conclude that androgens can stimulate human and murine osteoblastic cell proliferation in vitro, and induce expression of the osteoblast-line differentiation marker ALP, presumably by an androgen receptor mediated mechanism.

Studies of the mechanism by which androgens enhance mitogenesis and differentiation in bone cells.

Recently, we reported a direct effect of androgens on murine and human bone cells to stimulate bone cell proliferation and differentiation. To test whether this effect of androgenic steroids might be mediated by growth factors, we measured relative concentrations of insulin-like growth factor-I and -II (IGF-I and IGF-II) and transforming growth factor-beta (TGF beta) in the conditioned medium from androgen-treated murine calvarial cell cultures. Only the concentration of TGF beta was increased. Consistent with the increased secretion of TGF beta in the mouse calvarial cell system, we observed an increased expression of TGF beta mRNA in a normal human osteoblastic cell system. We also determined whether androgens alter the response to growth factors. We found that dihydrotestosterone (DHT) treatment enhanced the mitogenic effects of fibroblast growth factor (FGF) and IGF-II but not those of IGF-I. The enhanced effect of FGF and IGF-II after DHT pretreatment was not affected by addition of TGF beta-blocking antibodies or by changing the culture medium. This indicated that in addition to increased release of TGF beta, another mechanism might be involved in the action of DHT on human and murine bone cells. Thus, we investigated the binding of human IGF-II to human osteoblastic cells and observed an increase in IGF-II binding after DHT treatment. Our results are consistent with a mechanism of action of androgens on bone cells that involves the induction of TGF beta and, in addition, may sensitize the cells to show an enhanced response to FGF and IGF-II, possibly by changing the receptor binding of mitogenic growth factors.

Osteoporosis in eating disorders: a follow-up study of patients with anorexia and bulimia nervosa.

This study prospectively investigated the course of bone mineral density (BMD) in patients with anorexia nervosa (AN) and bulimia nervosa (BN) over a 3.6-yr follow-up period. From an initial sample of 47 female patients with an eating disorder (T1), 38 (n = 24 AN; n = 14 BN) were reassessed at follow-up (T2) (participation rate, 80.1%). For nonrecovered AN patients at T2, prevalence rates of osteopenia (-1.0 SD > or = T-score > -2.5 SD) and osteoporosis (T-score < or = -2.5 SD) at the lumbar spine were 54.2 and 20.8%, respectively. Due to an annual loss of lumbar spine BMD (-3.7 +/- 4.9%) in the chronic AN patients and a slight but insignificant annual increase (0.7 +/- 1.7%) for those who recovered, the difference in BMD between both outcome groups was more pronounced at follow-up (0.93 +/- 0.13 vs. 1.14 +/- 0.13 g/cm2; P < 0.01). Nonrecovered AN patients with binge eating/purging type showed a significantly reduced BMD compared with patients with the restricting type (0.87 +/- 0.13 vs. 1.02 +/- 0.08 g/cm2; P = 0.02). Both at baseline and follow-up, AN patients had increased rates of bone resorption, as measured by urinary desoxypyridinoline, compared with a control group (n = 42) (11.4 +/- 4.4 vs. 10.4 +/- 7.8, P < 0.001, vs. 5.6 +/- 2.4 and 10.4 +/- 7.8 nM/mM creatinine, P < 0.05, respectively). The subtype of AN and body mass index were best predictors for BMD at the lumbar spine at follow-up (R2 = 0.576). With one exception, all bulimic patients had BMD and markers of bone turnover within the normal range. These results suggest that patients with chronic AN, particularly of the binge eating/purging type, are at high risk for osteoporosis and may need additional therapy to prevent bone loss.

Human bone cell phenotypes differ depending on their skeletal site of origin.

This report describes skeletal site-related differences in human osteoblastic cell metabolism in studies of four patients. Northern analyses of the constitutive growth factor messenger ribonucleic acid (mRNA) expression pattern in mandibular and iliac crest-derived human osteoblastic cells (based on within-patient comparisons) revealed higher mRNA levels for strong mitogenic growth factors such as basic fibroblast growth factor (bFGF) and insulin-like growth factor II (IGF-II) in the rapidly proliferating and less alkaline phosphatase (ALP)-expressing mandibular osteoblastic cells compared to those in the lower bFGF and IGF-II mRNA levels in slowly proliferating iliac human osteoblastic cells exhibiting a higher ALP expression level. In contrast, transforming growth factor-beta (TGF beta) mRNA was more abundant in iliac human osteoblastic cells than in mandibular osteoblastic cells. Furthermore, we found that there was a proportionality, based on data from both sites, between the level of constitutive TGF beta mRNA and the response to exogenously administered bFGF or IGF-II. A comparable pattern of growth characteristics and mRNA expression was also observed in transformed human osteoblastic cells that had been subcloned in sublines expressing high and low levels of the human osteoblastic differentiation marker ALP. These findings are consistent with 1) skeletal site-related differences in human bone cell phenotypes, and 2) decreased IGF-II and bFGF expression and increased TGF beta expression and responsiveness to bFGF and IGF-II in human bone cells exhibiting a high ALP expression.

Effects of triiodothyronine on the insulin-like growth factor system in primary human osteoblastic cells in vitro.

Thyroid hormone plays a major role in the regulation of bone metabolism but the mechanism by which this is accomplished is not clear. Interactions of thyroid hormone with the growth hormone/insulin-like growth factors (IGFs) axis suggest an alternate pathway of action for triiodothyronine (T(3)) on bone formation, besides direct effects. The present study investigates the influence of T(3) on IGF-1, IGF-2, IGF-1 receptor (IGF-1R), and IGF binding protein (IGFBP) transcripts, and on IGF-1 action in human osteoblastic cells (hOB) under serum-free culture conditions. No influence of T(3) on IGF-1, IGF-2, IGFBP-3, or IGFBP-4 mRNA levels in hOB was observed. However, T(3) at concentrations of 10(-8) mol/L and 10(-7) mol/L increased IGF-1R mRNA levels in a dose-dependent manner (p < 0.01) and enhanced IGFBP-5 mRNA levels at a concentration of 10(-7) mol/L (p < 0.05), as assessed by reverse transcriptase-polymerase chain reaction. Correspondingly, Scatchard analysis of [(125)I]-IGF-1 binding revealed that T(3) at 10(-7) mol/L increased the number of IGF-1 binding sites in hOB, with small changes in receptor affinity. In addition, a synergistic effect of T(3) and IGF-1 on hOB proliferation was found (p < 0.05). We conclude that IGF-1R and IGFBP-5 are thyroid hormone target genes in human osteoblasts, whereas IGF-1 mRNA expression itself appears not to be regulated by T(3) in hOB. However, T(3) stimulates IGF-1R mRNA expression as well as IGF-1 binding and IGF-1 induced cell proliferation in osteoblasts, thus suggesting thyroid hormone may potentiate the effect of IGF-1 at the receptor level. This may contribute to the positive effects of thyroid hormone on bone formation, which, in addition, may be modulated by increased IGFBP-5 expression.