scholarly journals Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts

2002 ◽  
Vol 159 (1) ◽  
pp. 147-156 ◽  
Author(s):  
Toru Akune ◽  
Naoshi Ogata ◽  
Kazuto Hoshi ◽  
Naoto Kubota ◽  
Yasuo Terauchi ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Insulin Receptor ◽  
Intracellular Signaling ◽  
Bone Marrow Cells ◽  
Adenovirus Vector ◽  
Nuclear Factor Κb ◽  
Insulin Receptor Substrates ◽  
Anabolic Action ◽  
Igf I

Insulin receptor substrates (IRS-1 and IRS-2) are essential for intracellular signaling by insulin and insulin-like growth factor-I (IGF-I), anabolic regulators of bone metabolism. Although mice lacking the IRS-2 gene (IRS-2−/− mice) developed normally, they exhibited osteopenia with decreased bone formation and increased bone resorption. Cultured IRS-2−/− osteoblasts showed reduced differentiation and matrix synthesis compared with wild-type osteoblasts. However, they showed increased receptor activator of nuclear factor κB ligand (RANKL) expression and osteoclastogenesis in the coculture with bone marrow cells, which were restored by reintroduction of IRS-2 using an adenovirus vector. Although IRS-2 was expressed and phosphorylated by insulin and IGF-I in both osteoblasts and osteoclastic cells, cultures in the absence of osteoblasts revealed that intrinsic IRS-2 signaling in osteoclastic cells was not important for their differentiation, function, or survival. It is concluded that IRS-2 deficiency in osteoblasts causes osteopenia through impaired anabolic function and enhanced supporting ability of osteoclastogenesis. We propose that IRS-2 is needed to maintain the predominance of bone formation over bone resorption, whereas IRS-1 maintains bone turnover, as we previously reported; the integration of these two signalings causes a potent bone anabolic action by insulin and IGF-I.

scholarly journals Effect of mechanical loading on insulin-like growth factor-I gene expression in rat tibia

2007 ◽  
Vol 192 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Christianne M A Reijnders ◽  
Nathalie Bravenboer ◽  
Annechien M Tromp ◽  
Marinus A Blankenstein ◽  
Paul Lips
Keyword(s):  
Bone Formation ◽  
Mrna Expression ◽  
Mechanical Loading ◽  
Mechanical Stimulation ◽  
Molecular Mechanisms ◽  
Bone Marrow Cells ◽  
Mechanical Stimuli ◽  
Igf I ◽  
Female Wistar Rats ◽  
Tibia Shaft

Mechanical loading plays an essential role in maintaining skeletal integrity. Mechanical stimulation leads to increased bone formation. However, the cellular and molecular mechanisms that are involved in the translation of mechanical stimuli into bone formation, are not completely understood. Growth factors and osteocytes, which act as mechanosensors, play a key role during the bone formation after mechanical stimulation. The aim of this study was to characterize the role of IGF-I in the translation of mechanical stimuli into bone formation locally in rat tibiae. Fifteen female Wistar rats were randomly assigned to three groups (n = 5): load, sham-loaded, and control. The four-point bending model of Forwood and Turner was used to induce a single period of mechanical loading on the tibia shaft. The effects of mechanical loading on IGF-I mRNA expression were determined with non-radioactive in situ hybridization on decalcified tibiae sections, 6 h after the loading session. Endogenous IGF-I mRNA was expressed in trabecular and cortical osteoblasts, some trabecular and sub-endocortical osteocytes, intracortical endothelial cells of blood vessels, and periosteum. Megakaryocytes, macrophages, and myeloid cells also expressed IGF-I mRNA. In the growth plate, IGF-I mRNA was located in proliferative and hypertrophic chondrocytes. Mechanical loading did not affect the IGF-I mRNA expression in osteoblasts, bone marrow cells, and chondrocytes, but the osteocytes at the endosteal side of the shaft showed a twofold increase of IGF-I mRNA expression. The proportion of IGF-I mRNA positive osteocytes in loaded tibiae was 29.3 ± 12.9% (mean ± s.d.; n = 5), whereas sham-loaded and contra-lateral control tibiae exhibited 16.7 ± 4.4% (n = 5) and 14.7 ± 4.2% (n = 10) respectively (P < 0.05). Lamellar bone formation after a single mechanical loading session was observed at the endosteal side of the shaft. In conclusion, a single loading session results in a twofold up-regulation of IGF-I mRNA synthesis in osteocytes which are present in multiple layers extending into the cortical bone of mechanically stimulated tibia shaft 6 h after loading. This supports the hypothesis that IGF-I, which is located in osteocytes, is involved in the translation of mechanical stimuli into bone formation.

scholarly journals The emerging role of IMD 0354 on bone homeostasis by suppressing osteoclastogenesis and bone resorption, but without affecting bone formation

2019 ◽  
Vol 10 (9) ◽  
Author(s):  
Wenxiang Chen ◽  
Ziang Xie ◽  
Pan Tang ◽  
Yongli Wang ◽  
Zhiwei Jie ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Drug ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Bone Homeostasis

Abstract Osteoporosis is caused by an imbalance between bone formation and bone resorption. Receptor activator of nuclear factor-κB ligand (RANKL) promotes the activity and differentiation of osteoclasts via activating the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. IMD 0354 is a selective molecular inhibitor of inhibitor of NF-κB kinase subunit beta (IKKβ) and effective for treatment of acute and subacute inflammatory diseases through the suppression of NF-κB activation. However, the effect of IMD 0354 on bone homeostasis is unknown. In this study, we demonstrated that IMD 0354 significantly attenuated ovariectomy-induced bone loss and inhibited osteoclastogenesis in mice, whereas bone formation was not affected. Additionally, IMD 0354 dramatically inhibited osteoclast differentiation and function induced by RANKL and macrophage colony-stimulating factor in bone marrow monocytes as verified by tartrate-resistant acid phosphatase (TRAP) staining as well as bone resorption assay in vitro. Subsequently, we found that activation of NF-κB signaling and the ERK/c-Fos axis were blunted during osteoclast formation induced by RANKL. Transcription factors nuclear factor of activated T cells c1 (NFATc1) and c-Fos were suppressed with the decreased expression of osteoclast-related genes by IMD 0354. Our findings suggest that IMD 0354 could be a potential preventive and therapeutic drug for osteoporosis.

scholarly journals The Effects of Anorexia Nervosa on Bone Metabolism in Female Adolescents1

1999 ◽  
Vol 84 (12) ◽  
pp. 4489-4496 ◽  
Author(s):  
Leslie A. Soyka ◽  
Steven Grinspoon ◽  
Lynne L. Levitsky ◽  
David B. Herzog ◽  
Anne Klibanski
Keyword(s):  
Anorexia Nervosa ◽  
Bone Density ◽  
Bone Resorption ◽  
Bone Formation ◽  
Nutritional Status ◽  
Bone Metabolism ◽  
Lean Body Mass ◽  
Adolescent Girls ◽  
Igf I ◽  
The Mean

Osteopenia is a frequent, often persistent, complication of anorexia nervosa (AN) in adolescent girls and occurs during a critical time in bone development. Little is known about bone metabolism in this patient population. Therefore, we measured bone density (BMD) and body composition by dual energy x-ray absorptiometry, nutritional status, bone turnover, calcium, and hormonal status in 19 adolescent girls with AN (mean ± sem, 16.0 ± 0.4 yr) and 19 bone age-matched controls. The mean duration of AN was 19 ± 5 months. Spinal (L1–L4) osteopenia was common in AN. Lumbar anterioposterior BMD was more than 1 sd below the mean in 42% of patients, and lateral spine BMD was more than 1 sd below in 63% of patients compared with controls. Lean body mass significantly predicted lumbar bone mineral content (r = 0.75; P &lt; 0.0001) in controls only. In AN, duration of illness was the most significant predictor of spinal BMD (lumbar: r = −0.44; P = 0.06; lateral: r= −0.59; P = 0.008). AN adolescents with mature BA (15 yr and greater) were hypogonadal [estradiol, 16.2 ± 1.9 vs. 23.3 ± 1.6 pg/mL (P = 0.01); free testosterone, 0.70 ± 0.17 vs. 1.36 ± 0.14 pg/mL (P = 0.01)] although dehydroepiandrosterone sulfate and urinary free cortisol levels did not differ. Leptin levels were reduced in AN (2.9 ± 2.1 vs. 16.5 ± 1.8 ng/mL; P &lt; 0.0001). Insulin-like growth factor I (IGF-I) was reduced in AN to 50% of control levels (219 ± 41 vs. 511 ± 35 ng/mL; P &lt; 0.0001) and correlated with all measures of nutritional status, particularly leptin (r = 0.80; P &lt; 0.0001). Surrogate markers of bone formation, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP), were significantly (P = 0.02) reduced in AN vs. controls (OC, 39.1 ± 6.4 vs. 59.2 ± 5.2 ng/mL; BSAP, 27.9 ± 4.0 vs. 40.6 ± 3.4 U/L). The majority of the variation in bone formation in AN was due to IGF-I levels (OC: r2 = 0.72; P = 0.002; BSAP: r2 = 0.53; P = 0.01) in stepwise regression analyses. Bone resorption was comparable in patients and controls. These data demonstrate that bone formation is reduced and uncoupled to bone resorption in mature adolescents with AN in association with low bone density. Lean body mass was a significant predictor of BMD in controls, but not AN patients. The major correlate of bone formation in AN was the nutritionally dependent bone trophic factor, IGF-I. Reduced IGF-I during the critical period of bone mineral accumulation may be an important factor in the development of osteopenia in adolescents with AN.

Relation of RANKL and OPG Levels with Bone Resorption in Patients with Acromegaly and Prolactinoma

2018 ◽  
Vol 50 (07) ◽  
pp. 562-567 ◽  
Author(s):  
Firuzan Ozer ◽  
Selcuk Dagdelen ◽  
Tomris Erbas
Keyword(s):  
Bone Resorption ◽  
Inverse Correlation ◽  
Serum Levels ◽  
Nuclear Factor Κb ◽  
Control Group ◽  
Mineral Density ◽  
Compensatory Response ◽  
Positive Correlation ◽  
Igf I

AbstractThe objective of this study was to investigate the effect of hyperprolactinemia and high levels of insulin-like growth factor-I (IGF-I) on bone resorption and their relation with receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in patients with prolactinoma and acromegaly. Thirty-one patients with acromegaly, 28 patients with prolactinoma, and 33 healthy individuals were included in the study. Serum concentrations of RANKL, OPG, bone alkaline phosphatase (bone ALP), osteocalcin (OC), C-terminal telopeptide of type 1 collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and urine deoxypyridinoline (DPD) levels were detected and bone mineral density (BMD) was measured. Groups were not statistically different from each other with regard to serum levels of RANKL and OPG. The RANKL/OPG ratio was higher in the prolactinoma group than in the control group (p=0.046). A positive correlation between OPG and increasing age was detected in both the prolactinoma and control groups (r=0.524, p=0.004 and r=0.380, p=0.029, respectively). An inverse correlation was observed between IGF-I and OPG after excluding age in the prolactinoma group (r=–0.412, p=0.046). OC and bone ALP were negatively associated with RANKL in the acromegaly group (r=–0.384, p=0.036 and r=–0.528, p=0.003, respectively). There was an inverse correlation between OPG and BMD at the femoral neck in the acromegaly group (r=–0.422, p=0.02). The effect of IGF-I on bone remodeling may be partly mediated by RANKL and OPG. The RANKL/OPG ratio plays an important role in prolactinoma. A positive correlation of OPG with age and an inverse correlation with IGF-I favor the compensatory response of OPG against bone loss in the aging skeleton.

scholarly journals Insulin Receptor Substrate-1 Is Required for Bone Anabolic Function of Parathyroid Hormone in Mice

Endocrinology ◽  
2005 ◽  
Vol 146 (6) ◽  
pp. 2620-2628 ◽  
Author(s):  
Masayuki Yamaguchi ◽  
Naoshi Ogata ◽  
Yusuke Shinoda ◽  
Toru Akune ◽  
Satoru Kamekura ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Wild Type ◽  
Paracrine Factor ◽  
Protein Levels ◽  
Anabolic Action ◽  
Igf I ◽  
In The Wild ◽  
Biochemical Analyses

Abstract Bone anabolic action of PTH has been suggested to be mediated by induction of IGF-I in osteoblasts; however, little is known about the molecular mechanism by which IGF-I leads to bone formation under the PTH stimulation. This study initially confirmed in mouse osteoblast cultures that PTH treatment increased IGF-I mRNA and protein levels and alkaline phosphatase activity, which were accompanied by phosphorylations of IGF-I receptor, insulin receptor substrate (IRS)-1 and IRS-2, essential adaptor molecules for the IGF-I signaling. To learn the involvement of IRS-1 and IRS-2 in the bone anabolic action of PTH in vivo, IRS-1−/− and IRS-2−/− mice and their respective wild-type littermates were given daily injections of PTH (80 μg/kg) or vehicle for 4 wk. In the wild-type mice, the PTH injection increased bone mineral densities of the femur, tibia, and vertebrae by 10–20% without altering the serum IGF-I level. These stimulations were similarly seen in IRS-2−/− mice; however, they were markedly suppressed in IRS-1−/− mice. Although the PTH anabolic effects were stronger on trabecular bones than on cortical bones, the stimulations on both bones were blocked in IRS-1−/− mice but not in IRS-2−/− mice. Histomorphometric and biochemical analyses showed an increased bone turnover by PTH, which was also blunted by the IRS-1 deficiency, though not by the IRS-2 deficiency. These results indicate that the PTH bone anabolic action is mediated by the activation of IRS-1, but not IRS-2, as a downstream signaling of IGF-I that acts locally as an autocrine/paracrine factor.

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

2002 ◽  
pp. 339-348 ◽  
Author(s):  
T Sugimoto ◽  
H Kaji ◽  
D Nakaoka ◽  
M Yamauchi ◽  
S Yano ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Lumbar Spine ◽  
Side Effects ◽  
Bone Resorption ◽  
Bone Formation ◽  
Low Dose ◽  
Elderly Women ◽  
Serum Concentrations ◽  
Gh Treatment ◽  
Igf I

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.

scholarly journals Kruppel-like factor 4 attenuates osteoblast formation, function, and cross talk with osteoclasts

2014 ◽  
Vol 204 (6) ◽  
pp. 1063-1074 ◽  
Author(s):  
Jung Ha Kim ◽  
Kabsun Kim ◽  
Bang Ung Youn ◽  
Jongwon Lee ◽  
Inyoung Kim ◽  
...  
Keyword(s):  
Bone Formation ◽  
Osteoblast Differentiation ◽  
Target Genes ◽  
Bone Marrow Cells ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Conditional Knockout ◽  
Mouse Bone Marrow ◽  
Bone Homeostasis ◽  
Rankl Expression

Osteoblasts not only control bone formation but also support osteoclast differentiation. Here we show the involvement of Kruppel-like factor 4 (KLF4) in the differentiation of osteoclasts and osteoblasts. KLF4 was down-regulated by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in osteoblasts. Overexpression of KLF4 in osteoblasts attenuated 1,25(OH)2D3-induced osteoclast differentiation in co-culture of mouse bone marrow cells and osteoblasts through the down-regulation of receptor activator of nuclear factor κB ligand (RANKL) expression. Direct binding of KLF4 to the RANKL promoter repressed 1,25(OH)2D3-induced RANKL expression by preventing vitamin D receptor from binding to the RANKL promoter region. In contrast, ectopic overexpression of KLF4 in osteoblasts attenuated osteoblast differentiation and mineralization. KLF4 interacted directly with Runx2 and inhibited the expression of its target genes. Moreover, mice with conditional knockout of KLF4 in osteoblasts showed markedly increased bone mass caused by enhanced bone formation despite increased osteoclast activity. Thus, our data suggest that KLF4 controls bone homeostasis by negatively regulating both osteoclast and osteoblast differentiation.

scholarly journals Inhibition of markers of bone resorption by consumption of vitamin D and calcium-fortified soft plain cheese by institutionalised elderly women

2009 ◽  
Vol 102 (7) ◽  
pp. 962-966 ◽  
Author(s):  
Jean-Philippe Bonjour ◽  
Valérie Benoit ◽  
Olivier Pourchaire ◽  
Monique Ferry ◽  
Brigitte Rousseau ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Elderly Women ◽  
Bone Remodelling ◽  
Open Trial ◽  
Amino Terminal ◽  
Age Related ◽  
Igf I

Acceleration of bone remodelling increases the risk of fragility fractures. The objective of the present study was to explore in elderly women whether a vitamin D and Ca-fortified dairy product providing about 17–25 % of the recommended intakes in vitamin D, Ca and proteins would reduce secondary hyperparathyroidism and bone remodelling in a way that may attenuate age-related bone loss in the long term. Thirty-seven institutionalised women, aged 84·8 (sd 8·1) years, with low serum 25-hydroxyvitamin D (5·5 (sd 1·7) ng/ml) were enrolled into a multicentre open trial to consume during 1 month two servings of soft plain cheese made of semi-skimmed milk providing daily 686 kJ (164 kcal), 2·5 μg vitamin D, 302 mg Ca and 14·2 g proteins. The primary endpoint was the change in serum carboxy terminal cross-linked telopeptide of type I collagen (CTX), selected as a marker of bone resorption. Thirty-five subjects remained compliant. Mean serum changes were: 25-hydroyvitamin D, +14·5 % (P = 0·0051); parathyroid hormone (PTH), − 12·3 % (P = 0·0011); CTX, − 7·5 % (P = 0·01); tartrate-resistant acid phosphatase isoform 5b (TRAP 5b), − 9·9 % (P < 0·0001); albumin, +6·2 % (P < 0·0001); insulin-like growth factor-I (IGF-I),+16·9 % (P < 0·0001); osteocalcin, +8·3 % (P = 0·0166); amino-terminal propeptide of type 1 procollagen (P1NP),+19·3 % (P = 0·0031). The present open trial suggests that fortified soft plain cheese consumed by elderly women with vitamin D insufficiency can reduce bone resorption markers by positively influencing Ca and protein economy, as expressed by decreased PTH and increased IGF-I, respectively. The rise in the bone formation marker P1NP could be explained by a protein-mediated increase in IGF-I. Thus, such a dietary intervention might uncouple, at least transiently, bone resorption from bone formation and thereby attenuate age-related bone loss.

scholarly journals The bone remodelling cycle

2018 ◽  
Vol 55 (3) ◽  
pp. 308-327 ◽  
Author(s):  
JS Kenkre ◽  
JHD Bassett
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Disease ◽  
Molecular Mechanisms ◽  
Bone Remodelling ◽  
Nuclear Factor Κb ◽  
Pharmacological Interventions ◽  
Osteoblastic Bone Formation ◽  
Metabolic Bone ◽  
Tightly Coupled

The bone remodelling cycle replaces old and damaged bone and is a highly regulated, lifelong process essential for preserving bone integrity and maintaining mineral homeostasis. During the bone remodelling cycle, osteoclastic resorption is tightly coupled to osteoblastic bone formation. The remodelling cycle occurs within the basic multicellular unit and comprises five co-ordinated steps; activation, resorption, reversal, formation and termination. These steps occur simultaneously but asynchronously at multiple different locations within the skeleton. Study of rare human bone disease and animal models have helped to elucidate the cellular and molecular mechanisms that regulate the bone remodelling cycle. The key signalling pathways controlling osteoclastic bone resorption and osteoblastic bone formation are receptor activator of nuclear factor-κB (RANK)/RANK ligand/osteoprotegerin and canonical Wnt signalling. Cytokines, growth factors and prostaglandins act as paracrine regulators of the cycle, whereas endocrine regulators include parathyroid hormone, vitamin D, calcitonin, growth hormone, glucocorticoids, sex hormones, and thyroid hormone. Disruption of the bone remodelling cycle and any resulting imbalance between bone resorption and formation leads to metabolic bone disease, most commonly osteoporosis. The advances in understanding the cellular and molecular mechanisms underlying bone remodelling have also provided targets for pharmacological interventions which include antiresorptive and anabolic therapies. This review will describe the remodelling process and its regulation, discuss osteoporosis and summarize the commonest pharmacological interventions used in its management.

Prolonged intermittent but not continuous administration of oestradiol-17β increases bone volume in the rat

1993 ◽  
Vol 139 (2) ◽  
pp. 267-NP ◽  
Author(s):  
J. H. Tobias ◽  
A. Gallagher ◽  
T. J. Chambers
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Volume ◽  
Female Rats ◽  
Continuous Treatment ◽  
Prolonged Treatment ◽  
Continuous Administration ◽  
Anabolic Action ◽  
Important Stimulus

ABSTRACT We have previously found that administration of oestradiol-17β (OE2) to intact adult female rats of 19 days stimulates cancellous bone formation. However, this effect is not observed following longer periods of OE2 treatment, suggesting that the responsiveness of the skeleton to oestrogen's anabolic action is reduced after prolonged administration. A possible explanation for this is that oestrogen also suppresses bone resorption, which is an important stimulus for bone formation. We therefore investigated the effect of omitting OE2 for short periods, on the proximal tibial metaphysis of intact female rats. We found that, unlike continuous treatment with OE2 (40 pg/kg) for 56 days, omission of OE2 for 4 days out of every 20 was associated with a significant increase in cancellous bone volume. Although continuous and intermittent OE2 were both associated with a reduction in osteoclast surface, a decrease in the proportion of double fluorochrome-labelled surface was only seen after continuous OE2 treatment. We then studied the effects of longer periods of OE2 omission by giving OE2 (40 pg/kg) for three repeated cycles of: (1) OE2 for 16 days/vehicle for 4 days, (2) OE2 for 12 days/vehicle for 8 days, (3) OE2 for 8 days/vehicle for 12 days, or (4) OE2 for 4 days/vehicle for 16 days. We found a significant increase in cancellous bone volume when OE2 was stopped for either 4 or 8 days at a time. However, longer periods of OE2 omission did not affect bone volume, possibly because these were associated with an increase in bone resorption and/or a reduction in bone formation during the OE2-free period. In conclusion, we observed an increase in cancellous bone volume after prolonged treatment with oestrogen only if OE2 was omitted for short periods. This may be due, at least in part, to bone formation being maintained at a higher rate by such treatment than by either continuous OE2 administration or by intermittent administration where OE2 is discontinued for longer periods. Journal of Endocrinology (1993) 139, 267–273

Sign in / Sign up

Export Citation Format

Share Document