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Effect of Bone Morphogenetic Protein (BMP)-2 and BMP-7 on bone metabolism in Thyroid-Parathyroid Deprivated (TPTX) rats
Abstracts / Bone 44 (2009) S253–S338
Similar concentrations and combinations of BMPs were used to assess their potential to enhance osteogenic differentiation in bone marrow stromal cells using a mineralization assay and real-time PCR analysis of collagen type 1, runx2 and osterix as well as RANKL and OPG. The presented data show that the combination of BMP-2, BMP-5 and BMP-6 did not enhance osteoclastogenesis compared to the single use of either BMP. This was also reflected by the RANKL/OPG ratio at mRNA level which did not increase after treatment with all three BMPs. However, the effects of BMP-2, BMP-5 and BMP-6 in combination on osteoblast differentiation was additive. Also, mRNA expression levels of collagen type 1, runx2 and osterix were enhanced when exposed to BMP-2, BMP-5 and BMP-6 compared to the single use of either BMP. In conclusion, this study demonstrates that the combination of BMP-2, BMP-5 and BMP-6 stimulates osteoblasts while it reduces osteoclastogenesis. Thus, the synergistic use of various BMPs might improve efficacious bone regeneration in a clinical setting. This work was supported by the Camlog foundation. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.642
P217 Effect of outer membrane protein of treponema denticola on osteoclast formation M. Kima,*, H. Junb, S. Kima, B. Choib, J. Chaa, Y. Yooa a Department of Oral Biology, BK21 Project, Oral Science Research Center, Yonsei University College of Dentistry b Department of Oral Microbiology and Immunology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, South Korea Periodontitis is a chronic inflammatory disease in periodontal tissue with bacterial etiology. Alveolar bone resorption observed in periodontitis is a non-reversible hard-tissue destruction which results in severe oral dysfunction. Previous studies to identify underlying pathogenic mechanisms of periodontitis have revealed the implication of oral spirochetes in associate with increased severity of periodontitis. Treponema denticola is one of the representative oral spirochetes. Outer membrane protein (OMP) of T. denticola is a molecule involved in the first stage of host-bacterium interaction. The aim of this study is to investigate the effect of T. denticola OMP on osteoclast formation. In order to observe osteoclast formation by OMP, mouse bone marrow cells were co-cultured with mouse calvaria-derived osteoblasts. The number of osteoclasts was determined by TRAP staining. RANKL and PGE2 expression stimulated by OMP in osteoblasts was measured by ELISA. Escherichia coli LPS was used as a positive control in each experiment. In co-cultures, osteoclasts were formed in response to OMP (1–12.5 \mug/ml) in dose-dependent manner as well as to LPS (0.001–10 \mug/ml). This osteoclast formation was completely suppressed by OPG or NS398 (cyclooxygenase-2 inhibitor). In protein level, OMP of T. denticola or LPS elevated RANKL and PGE2 expression in osteoblasts and thses up-regulated expressions were strongly inhibited by NS398. These results suggest that OMP of T. denticola acts as an inducer in osteoclast formation and that OMP-induced osteoclast formation is stimulated by PGE2-mediated RANKL expression. Therefore, OMP of T. denticola may play an important role in alveolar bone resorption in periodontitis. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.643
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P218 Relationship of osteoclast resorption activity and bone surface roughness M. Rumplera,*, P. Roschgera, R. Weinkamerb, J. Dunlopb, P. Fratzlb, K. Klaushofera a Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, Vienna, Austria b Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany Throughout our lifetime, bone is continuously removed and new bone is deposited in a process called “bone remodelling”. By this process the structural integrity of the skeleton is maintained and its functional adaptation to the requirements is guaranteed. Two cell populations are responsible for this process: the osteoclasts, which resorb the old bone, and the osteoblasts, which deposit new bone. In order to understand remodelling, it is necessary to know how these to cell types react to topographical changes and for this it is helpful to look at both parts of the process separately. In previous we have investigated the process of tissue formation by osteoblasts in vitro in three-dimensional scaffolds with controlled architecture. We have shown that osteoblasts respond to their local geometrical environment. In case of osteoclasts it is known that they are able to sense local properties of the underlying substrate reflected in a reorganization of their podosomes. Furthermore, the fact that roughness of bone affects polarity of osteoclasts may indicate sensitivity of these cells for bone damage as well. In this project we are going to answer the question if bone topography and surface modification may influence the resorption behaviour of osteoclasts beyond biochemical and mechanical signals. For this purpose we isolated murine osteoclasts from mouse bone marrow and seeded them onto cortical bovine bone slices of a thickness of approximately 500 μm. These bone slices exhibited either a “rough” surface (as obtained from diamond saw) or polished surfaces (as obtained by polishing with tissue of 3 μm grain size). Cultures were kept for 14 days and resorption areas were determined afterwards. All resorption areas were normalized to bone areas and values from polished slices were set to 1. In our quantitative analyses of the resorption behaviour of osteoclasts due to various surface roughness on cortical bone, we found a 2.8 to 7.3-fold higher resorption activity from osteoclasts on rough surfaces compared to the corresponding value on the polished surface. These data strongly indicate that surface topography plays a crucial role in resorption activity of osteoclasts including all preceding steps like acquisition, attachment and differentiation of precursor cells. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.644
P219 Effect of Bone Morphogenetic Protein (BMP)-2 and BMP-7 on bone metabolism in Thyroid-Parathyroid Deprivated (TPTX) rats N. Dracaa,*, P. Simica, A. Tikvicaa, D. Rogicb, I. Dumica, S. Vukicevica a Laboratory for Mineralized Tissues, School of Medicine, University of Zagreb b Department for Laboratory Diagnostics, Clinical Hospital Center Zagreb, Zagreb, Croatia BMP-2 and -7 have been successfully used in patients with long bone fractures, non-unions and spinal fusions. However, the magnitude of their systemic effect on bone formation and resorption, especially in rats lacking calciotropic hormones, is not known. We
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Abstracts / Bone 44 (2009) S253–S338
explored the resorptive effect of BMP-2 and -7 on the bone in 6 months old male Sprague-Dawley rats which were surgically thyroparathyroidectomized (TPTx). BMP-2 and -7 therapy was initiated 7 days following TPTx and administered daily for 2 weeks for each BMP as follows: (1) Sham, (2) TPTx+ vehicle, (3) TPTx+BMP 10 μg/kg, (4) TPTx+BMP 70 μg/kg, (5) TPTx+ BMP 250 μg/kg. The surgery resulted in hypocalcemia and hyperphosphatemia due to the lack of PTH. BMP-2 treatment with all doses had an additional effect on increasing the calcium and decreasing the phosphate serum levels similar to sham levels, with the BMP-2 250 μg/kg dose being the most effective. BMP-7 therapy had no effect on both serum calcium or phosphate level, suggesting that BMP-2 effect on bone resorption was more pronounced. TPTx also resulted in a decrease of C-telopeptide serum levels 48 h after surgery. BMP-2 administration stimulated bone resorption at 24 h by increasing CTx as compared to both sham and TPTx rats. BMP-7 at 70 μg and 250 μg stimulated the bone resorption on day 14 as compared to both sham (58%, 86%) and TPTx (55%, 83%) rats. In BMP-2 treated rats osteocalcin (OC) remained low while in rats treated with BMP7 (250 μg/kg) serum OC was increased on day 14. BMP-2 increased RANKL serum values, while BMP-7 increased the osteoprotegerin in serum, with the highest dose being the most effective. MicroCT analyses of the distal femur showed that both BMP-2 and 7 treatment increased the trabecular bone volume as compared to TPTx rats, with BMP-2 being more effective. Both BMPs had the same effect on the trabecular pattern formation decreasing it below the sham levels. While BMP-7 had no effect on other measured parameters, BMP-2 also decreased the trabecular separation and increased the trabecular number to the sham levels. We conclude that in lack of calciotropic hormones both BMP-2 and BMP-7 equally increase bone volume via different mechanisms of action, while BMP-2 was more efficient in promoting bone resorption. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.645
P220 Alendronate reduces osteoclast activity and formation through the reduction of rankl and osteoclast precursors in osteoporotic women P. D'Amelioa,*, A. Grimaldia, M.A. Cristofaroa, M. Ravazzolia, G.P. Pescarmonab, G. Isaiaa a Internal Medicine b Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Italy Bisphosphonates are directed against osteoclasts, but it is still unclear which of the steps of osteoclast formation and activity are most sensitive to these drugs.The present study evaluates the effect of in vivo alendronate on osteoclastogenesis, cytokine production and bone resorption in postmenopausal women. Thirthy osteoporotic women were enrolled in the study: 15 patients were pre-treated with alendronate 70 mg/week while 15 were treated with calcium 1 g/day and vitamin D 800 UI/day, after three months the entire cohort received alendonate 70/mg, vitamin D 2800 UI/week and calcium 1 g/day for 12 months (combined therapy). The following parameters were assessed: changes in bone resorption, circulating osteoclast precursors, osteoclasts formation by peripheral blood mononuclear cells cultures, their vitality and variations in the production of cytokines before and after therapy. After 3 months of alendronate there is no significant reduction in the number of osteoclast precursors, osteoclast formation and vitality and in the level of cytokines in cultures and in serum, while there was
a significant reduction of in vivo bone resorption. An increase in TNF alpha was found after 3 months of alendronate therapy in the culture, while after year's combined therapy TNF alpha levels returned to baseline levels. These data could indicate an early inflammatory effect of alendronate and confirm previous data from an invivo animal study and in vitro studies with human cells suggesting that alendronate can increase TNF production from T cells. However, it is important to point out that a systemic increase in the TNF alpha levels or acute phasereaction was not observed in these patients, moreover the observed increase in TNF alpha was transitory since TNF returned to baseline in the year's. Year's therapy with alendronate plus calcium and vitamin D progressively reduces osteoclast precursors, osteoclast formation and serum RANKL Founding sources: This work was supported by an unconditioned grant from the Merck Sharp and Dohme SpA Italy and a grant from the Fondazione Internazionale Ricerche Medicina Sperimentale (FIRMS) Compagnia San Paolo. Conflict of interest: The work was supported by an unconditioned grant from the Merck Sharp and Dohme SpA Italy. doi:10.1016/j.bone.2009.03.646
P221 Oral calcitonin reduces cartilage erosion in an oa rat model with both traumatic injury and increased subchondral bone turnover R.H. Nielsena,*, B.C. Sondergaardb, I. Byrjalsenb, C. Christiansenb, M.A. Karsdalb a Pharmacology b Research and Development, Nordic Bioscience, Herlev, Denmark Background: Increased bone turnover, as caused by estrogen deficiency, has been speculated to augment the severity of cartilage erosion and to accelerate the pathogenesis of OA. An optimal intervention strategy for OA may therefore ideally target both bone and cartilage mal metabolisms. Calcitonin has been shown to affect both osteoclasts and chondrocytes. We investigated whether a novel oral formulation of salmon calcitonin could reduce cartilage erosion and attenuate osteophyte formation, observed secondary to induction of OA by combined partial medial meniscectomy and ovariectomy of rats. Methods: Four groups of 6 months old rats were subjected to sham, ovariectomy (OVX) or a combined ovariectomy and partial medial meniscectomy (OVX+MNX) and administered twice daily with oral salmon calcitonin(CT) (150 mg/kg 5-CNAC+ 2 mg/kg calcitonin) or vehicle control(V) (150 mg/kg 5-CNAC) in the following way: 1)Sham+V; 2)OVX+V; 3)OVX+MNX+V; 4)OVX +MNX+CT. C-terminal telopeptide of type II collagen (CTX-II) was measured in serum. At termination 8 weeks after surgery, the tibia was processed for histology, and articular cartilage area was measured within pre-defined compartments (medial, central and lateral) of the tibial plateau. Osteophyte area in the lateral compartment was recorded separately. Results: Calcitonin reduced erosion of the articular cartilage by 77% (p < 0.05), from 79.2% in the MNX+OVX group to 95.3% in the MNX+OVX+CT group, compared to sham animals. Ovariectomy alone resulted in a moderate 3.9% cartilage loss (NS). The area of osteophytes decreased 33% as a result of treatment with calcitonin. OVX surgery, but not meniscectomy, increased systemic CTX-II that was efficiently reduced (p < 0.05) when calcitonin was administered. Conclusion: Currently there are no treatments available for OA. These data are the first to demonstrate that an oral formulation of calcitonin protects against cartilage erosion and osteophyte formation in an in vivo OA model with both traumatic injury
Similar concentrations and combinations of BMPs were used to assess their potential to enhance osteogenic differentiation in bone marrow stromal cells using a mineralization assay and real-time PCR analysis of collagen type 1, runx2 and osterix as well as RANKL and OPG. The presented data show that the combination of BMP-2, BMP-5 and BMP-6 did not enhance osteoclastogenesis compared to the single use of either BMP. This was also reflected by the RANKL/OPG ratio at mRNA level which did not increase after treatment with all three BMPs. However, the effects of BMP-2, BMP-5 and BMP-6 in combination on osteoblast differentiation was additive. Also, mRNA expression levels of collagen type 1, runx2 and osterix were enhanced when exposed to BMP-2, BMP-5 and BMP-6 compared to the single use of either BMP. In conclusion, this study demonstrates that the combination of BMP-2, BMP-5 and BMP-6 stimulates osteoblasts while it reduces osteoclastogenesis. Thus, the synergistic use of various BMPs might improve efficacious bone regeneration in a clinical setting. This work was supported by the Camlog foundation. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.642
P217 Effect of outer membrane protein of treponema denticola on osteoclast formation M. Kima,*, H. Junb, S. Kima, B. Choib, J. Chaa, Y. Yooa a Department of Oral Biology, BK21 Project, Oral Science Research Center, Yonsei University College of Dentistry b Department of Oral Microbiology and Immunology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, South Korea Periodontitis is a chronic inflammatory disease in periodontal tissue with bacterial etiology. Alveolar bone resorption observed in periodontitis is a non-reversible hard-tissue destruction which results in severe oral dysfunction. Previous studies to identify underlying pathogenic mechanisms of periodontitis have revealed the implication of oral spirochetes in associate with increased severity of periodontitis. Treponema denticola is one of the representative oral spirochetes. Outer membrane protein (OMP) of T. denticola is a molecule involved in the first stage of host-bacterium interaction. The aim of this study is to investigate the effect of T. denticola OMP on osteoclast formation. In order to observe osteoclast formation by OMP, mouse bone marrow cells were co-cultured with mouse calvaria-derived osteoblasts. The number of osteoclasts was determined by TRAP staining. RANKL and PGE2 expression stimulated by OMP in osteoblasts was measured by ELISA. Escherichia coli LPS was used as a positive control in each experiment. In co-cultures, osteoclasts were formed in response to OMP (1–12.5 \mug/ml) in dose-dependent manner as well as to LPS (0.001–10 \mug/ml). This osteoclast formation was completely suppressed by OPG or NS398 (cyclooxygenase-2 inhibitor). In protein level, OMP of T. denticola or LPS elevated RANKL and PGE2 expression in osteoblasts and thses up-regulated expressions were strongly inhibited by NS398. These results suggest that OMP of T. denticola acts as an inducer in osteoclast formation and that OMP-induced osteoclast formation is stimulated by PGE2-mediated RANKL expression. Therefore, OMP of T. denticola may play an important role in alveolar bone resorption in periodontitis. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.643
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P218 Relationship of osteoclast resorption activity and bone surface roughness M. Rumplera,*, P. Roschgera, R. Weinkamerb, J. Dunlopb, P. Fratzlb, K. Klaushofera a Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, Vienna, Austria b Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany Throughout our lifetime, bone is continuously removed and new bone is deposited in a process called “bone remodelling”. By this process the structural integrity of the skeleton is maintained and its functional adaptation to the requirements is guaranteed. Two cell populations are responsible for this process: the osteoclasts, which resorb the old bone, and the osteoblasts, which deposit new bone. In order to understand remodelling, it is necessary to know how these to cell types react to topographical changes and for this it is helpful to look at both parts of the process separately. In previous we have investigated the process of tissue formation by osteoblasts in vitro in three-dimensional scaffolds with controlled architecture. We have shown that osteoblasts respond to their local geometrical environment. In case of osteoclasts it is known that they are able to sense local properties of the underlying substrate reflected in a reorganization of their podosomes. Furthermore, the fact that roughness of bone affects polarity of osteoclasts may indicate sensitivity of these cells for bone damage as well. In this project we are going to answer the question if bone topography and surface modification may influence the resorption behaviour of osteoclasts beyond biochemical and mechanical signals. For this purpose we isolated murine osteoclasts from mouse bone marrow and seeded them onto cortical bovine bone slices of a thickness of approximately 500 μm. These bone slices exhibited either a “rough” surface (as obtained from diamond saw) or polished surfaces (as obtained by polishing with tissue of 3 μm grain size). Cultures were kept for 14 days and resorption areas were determined afterwards. All resorption areas were normalized to bone areas and values from polished slices were set to 1. In our quantitative analyses of the resorption behaviour of osteoclasts due to various surface roughness on cortical bone, we found a 2.8 to 7.3-fold higher resorption activity from osteoclasts on rough surfaces compared to the corresponding value on the polished surface. These data strongly indicate that surface topography plays a crucial role in resorption activity of osteoclasts including all preceding steps like acquisition, attachment and differentiation of precursor cells. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.644
P219 Effect of Bone Morphogenetic Protein (BMP)-2 and BMP-7 on bone metabolism in Thyroid-Parathyroid Deprivated (TPTX) rats N. Dracaa,*, P. Simica, A. Tikvicaa, D. Rogicb, I. Dumica, S. Vukicevica a Laboratory for Mineralized Tissues, School of Medicine, University of Zagreb b Department for Laboratory Diagnostics, Clinical Hospital Center Zagreb, Zagreb, Croatia BMP-2 and -7 have been successfully used in patients with long bone fractures, non-unions and spinal fusions. However, the magnitude of their systemic effect on bone formation and resorption, especially in rats lacking calciotropic hormones, is not known. We
S336
Abstracts / Bone 44 (2009) S253–S338
explored the resorptive effect of BMP-2 and -7 on the bone in 6 months old male Sprague-Dawley rats which were surgically thyroparathyroidectomized (TPTx). BMP-2 and -7 therapy was initiated 7 days following TPTx and administered daily for 2 weeks for each BMP as follows: (1) Sham, (2) TPTx+ vehicle, (3) TPTx+BMP 10 μg/kg, (4) TPTx+BMP 70 μg/kg, (5) TPTx+ BMP 250 μg/kg. The surgery resulted in hypocalcemia and hyperphosphatemia due to the lack of PTH. BMP-2 treatment with all doses had an additional effect on increasing the calcium and decreasing the phosphate serum levels similar to sham levels, with the BMP-2 250 μg/kg dose being the most effective. BMP-7 therapy had no effect on both serum calcium or phosphate level, suggesting that BMP-2 effect on bone resorption was more pronounced. TPTx also resulted in a decrease of C-telopeptide serum levels 48 h after surgery. BMP-2 administration stimulated bone resorption at 24 h by increasing CTx as compared to both sham and TPTx rats. BMP-7 at 70 μg and 250 μg stimulated the bone resorption on day 14 as compared to both sham (58%, 86%) and TPTx (55%, 83%) rats. In BMP-2 treated rats osteocalcin (OC) remained low while in rats treated with BMP7 (250 μg/kg) serum OC was increased on day 14. BMP-2 increased RANKL serum values, while BMP-7 increased the osteoprotegerin in serum, with the highest dose being the most effective. MicroCT analyses of the distal femur showed that both BMP-2 and 7 treatment increased the trabecular bone volume as compared to TPTx rats, with BMP-2 being more effective. Both BMPs had the same effect on the trabecular pattern formation decreasing it below the sham levels. While BMP-7 had no effect on other measured parameters, BMP-2 also decreased the trabecular separation and increased the trabecular number to the sham levels. We conclude that in lack of calciotropic hormones both BMP-2 and BMP-7 equally increase bone volume via different mechanisms of action, while BMP-2 was more efficient in promoting bone resorption. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.645
P220 Alendronate reduces osteoclast activity and formation through the reduction of rankl and osteoclast precursors in osteoporotic women P. D'Amelioa,*, A. Grimaldia, M.A. Cristofaroa, M. Ravazzolia, G.P. Pescarmonab, G. Isaiaa a Internal Medicine b Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Italy Bisphosphonates are directed against osteoclasts, but it is still unclear which of the steps of osteoclast formation and activity are most sensitive to these drugs.The present study evaluates the effect of in vivo alendronate on osteoclastogenesis, cytokine production and bone resorption in postmenopausal women. Thirthy osteoporotic women were enrolled in the study: 15 patients were pre-treated with alendronate 70 mg/week while 15 were treated with calcium 1 g/day and vitamin D 800 UI/day, after three months the entire cohort received alendonate 70/mg, vitamin D 2800 UI/week and calcium 1 g/day for 12 months (combined therapy). The following parameters were assessed: changes in bone resorption, circulating osteoclast precursors, osteoclasts formation by peripheral blood mononuclear cells cultures, their vitality and variations in the production of cytokines before and after therapy. After 3 months of alendronate there is no significant reduction in the number of osteoclast precursors, osteoclast formation and vitality and in the level of cytokines in cultures and in serum, while there was
a significant reduction of in vivo bone resorption. An increase in TNF alpha was found after 3 months of alendronate therapy in the culture, while after year's combined therapy TNF alpha levels returned to baseline levels. These data could indicate an early inflammatory effect of alendronate and confirm previous data from an invivo animal study and in vitro studies with human cells suggesting that alendronate can increase TNF production from T cells. However, it is important to point out that a systemic increase in the TNF alpha levels or acute phasereaction was not observed in these patients, moreover the observed increase in TNF alpha was transitory since TNF returned to baseline in the year's. Year's therapy with alendronate plus calcium and vitamin D progressively reduces osteoclast precursors, osteoclast formation and serum RANKL Founding sources: This work was supported by an unconditioned grant from the Merck Sharp and Dohme SpA Italy and a grant from the Fondazione Internazionale Ricerche Medicina Sperimentale (FIRMS) Compagnia San Paolo. Conflict of interest: The work was supported by an unconditioned grant from the Merck Sharp and Dohme SpA Italy. doi:10.1016/j.bone.2009.03.646
P221 Oral calcitonin reduces cartilage erosion in an oa rat model with both traumatic injury and increased subchondral bone turnover R.H. Nielsena,*, B.C. Sondergaardb, I. Byrjalsenb, C. Christiansenb, M.A. Karsdalb a Pharmacology b Research and Development, Nordic Bioscience, Herlev, Denmark Background: Increased bone turnover, as caused by estrogen deficiency, has been speculated to augment the severity of cartilage erosion and to accelerate the pathogenesis of OA. An optimal intervention strategy for OA may therefore ideally target both bone and cartilage mal metabolisms. Calcitonin has been shown to affect both osteoclasts and chondrocytes. We investigated whether a novel oral formulation of salmon calcitonin could reduce cartilage erosion and attenuate osteophyte formation, observed secondary to induction of OA by combined partial medial meniscectomy and ovariectomy of rats. Methods: Four groups of 6 months old rats were subjected to sham, ovariectomy (OVX) or a combined ovariectomy and partial medial meniscectomy (OVX+MNX) and administered twice daily with oral salmon calcitonin(CT) (150 mg/kg 5-CNAC+ 2 mg/kg calcitonin) or vehicle control(V) (150 mg/kg 5-CNAC) in the following way: 1)Sham+V; 2)OVX+V; 3)OVX+MNX+V; 4)OVX +MNX+CT. C-terminal telopeptide of type II collagen (CTX-II) was measured in serum. At termination 8 weeks after surgery, the tibia was processed for histology, and articular cartilage area was measured within pre-defined compartments (medial, central and lateral) of the tibial plateau. Osteophyte area in the lateral compartment was recorded separately. Results: Calcitonin reduced erosion of the articular cartilage by 77% (p < 0.05), from 79.2% in the MNX+OVX group to 95.3% in the MNX+OVX+CT group, compared to sham animals. Ovariectomy alone resulted in a moderate 3.9% cartilage loss (NS). The area of osteophytes decreased 33% as a result of treatment with calcitonin. OVX surgery, but not meniscectomy, increased systemic CTX-II that was efficiently reduced (p < 0.05) when calcitonin was administered. Conclusion: Currently there are no treatments available for OA. These data are the first to demonstrate that an oral formulation of calcitonin protects against cartilage erosion and osteophyte formation in an in vivo OA model with both traumatic injury