Methylprednisone and Thiazolidinone Treatment Alter Bone Metabolism and Strength in Young Male and Female Rats

Abstracts mineralized trabecular width was seen in 6 of 11 biopsies. Diffuse label was noted in 5 of 11 biopsies. Mineralization abnormalities were noted in a significant number of patients with radiographic features of AFF. All of the women had normal or mildly reduced serum vitamin D levels. Conclusion: Histomorphometric features seen on bone biopsy in women sustaining an AFF in association with long term bisphosphonate use included evidence of mineralization abnormalities and decreased bone formation. 1 patient had features of decreased bone formation and mineralization abnormalities with only 5 months of bisphosphonate exposure. Improved understanding of the pathophysiology leading to these fractures may be gained with further histomorphometric data in larger numbers of patients. Disclosure of Interest: A. Khan Contract with: Amgen, Merck, NPS, A. Cheung Royalty from: Amgen, Eli Lilly, Warner Chilcott, Consultant for: Amgen, Eli Lilly, Merck, Warner Chilcott, Contract with: Amgen, Eli Lilly, Merck, O. Khan: None Declared, Z. Rahman: None Declared, K. Pritzker: None Declared, B. Lentle: None Declared

P101 MECHANICAL-LOADING THROUGH PASSIVE WEIGHBEARING AND ARTIFICIAL ELECTRICAL STIMULATION PREVENT AND EVEN REVERT SCI-INDUCED BONE LOSS QUALITY A. Zamarioli1,2,*, D. A. C. Maranho2, R. A. Battaglino1,3, L. R. Morse1,4,5, J. B. Volpon2, A. C. Shimano2; 1Department of Cytokine Biology, The Forsyth Institute, Cambridge, United States, 2Biomechanics, Medicine and Rehabilitation, University of Sao Paulo, Ribeirao Preto, Brazil, 3Department of Oral Medicine, Infection, and Immunity, 4Department of Physical Medicine and Rehabilitation, Harvard Medical School, 5Spaulding Rehabilitation Hospital, Boston, United States Aims: Injuries to the central nervous system such as spinal cord injury (SCI) often lead to rapid and extensive hindlimb bone loss due to the incapacity to bear weight and to contract muscles. To assess the effects of passive standing (PS), PS associated with vibration therapy (PS+VT) and electrical stimulation (ES) on bone quality in SCI rats. Methods: Male Wistar rats were divided into ten groups (n58/group). The first five groups were followed by 33 days after surgery [(1) Sham 33d, (2) SCI 33d, (3) SCI+PS 33d, (4) SCI+FES 33d], (5) SCI+PS+VT33d whence therapies were initiated on day 3 after SCI in order to simulate the administration of the rehabilitation programs as preventive tools against SCI-induced bone loss. The other five groups were followed by 63 days after surgery [(6) Sham 63d, (7) SCI 63d, (8) SCI+PS 63d and, (9) SCI+FES 63d, (10) SCI+PS+VT 63d] and therapies began on day 33 as methods to revert the bone loss induced by the SCI. Same rehabilitation protocol was used in all therapy groups and consisted of 20 minutes of session, three times a week for 30 days. At the end of each time point study, animals were weighted, allowing the comparison of body mass. Rats were then euthanized and bones were submitted to anatomical macroscopic analysis and microscopic assessment by scanning electronic microscopy (SEM) and mCT. Bone strength, BMD and serum bone markers were also assessed. Comparisons among groups were statistically processed by ANOVA followed by Tukey’s post hoc analysis. Level of significance was set at p!0.05. Results: SCI rats gained weight along the study, but at lower degree than Sham operated animals. SCI resulted in expressive and significant changes on bones tissue, causing anatomical changes, which were ameliorated and even reverted by artificial muscle contraction and weight-bearing. These finding corroborated with the increased bone strength, bone mass and bone formation within therapies. At the microscopic level, SEM and mCT images showed lower and thinner trabecular bone, with more spacing in between, which might be consisted with the increased fracture risk in the SCI population. PS, PS+VT and FES were efficient at ameliorating bone microarchitecture deterioration by thickening and increasing trabeculae. Conclusion: SCI caused detrimental changes in the macro and microscopic anatomy of the bone tissue, whereas both mechanical loading through weight-bearing and muscle contraction through electrical stimulation are efficient at ameliorating and even reverting the normal anatomy of the long bones and their quality in mass, strength, structure and metabolism. Acknowledgement: This work was supported and founded by Foundation for Research Support of the State of S~ao Paulo (FAPESP). Disclosure of Interest: None Declared

403 P102 METHYLPREDNISONE AND THIAZOLIDINONE TREATMENT ALTER BONE METABOLISM AND STRENGTH IN YOUNG MALE AND FEMALE RATS C. M. Bagi*, E. Berryman, C. Andresen; Comparative Medicine, Pfizer, Groton, United States Aims: The aim of this study was to assess impact of methylprednisone and thiazolidinone on bone metabolism, structure and strength in rapidly growing rats. Methods: In this study, to represent the clinical context in which the adverse effects of CS and TZDs on bone have been observed, we assessed the effect of methylprednisone and a thiazolidinone on bone properties in young male and female rats. Seven weeks old male and female Wistar rats were divided into 3 groups: Group 1 received vehicle, Group 2 received methylprednisone (MP, 5 mg/kg/day) and Group 3 received a thiazolidinone (TZD, 4 mg/kg/day). All rats were dosed 5 days/week and were bled at day -1 and day 42 for assessment of bone metabolism biomarkers including Osteocalcin, P1NP, CTX and TRAP5b. Femur and tibiae were collected at necropsy on day 42. Bone mass and structure at both the cortical and cancellous bone compartments were measured using mCT and pQCT. The 3-point bending method was used to measure cortical bone strength and dynamic bone histomorphometry and paraffin histology was deployed for evaluation of cellular events; bone formation and resorption. Results: Treatment with MP had a negative impact on body weight and bone growth in both male and female rats. While accumulation of cancellous bone in the area of primary and secondary spongiosa was evident in MP treated rats, there was a loss of cancellous bone in thiazolidinone treated rats. Cortical bone geometry and strength were also negatively impacted in both MP and TZD treated rats; however, the effect was greater in the MP group. The observed effects were greater in males than females because skeletal modeling was more prevalent in the males. Conclusion: Our data demonstrate that even though both drugs can negatively impact bone metabolism, the pathophysiology of bone loss is different between the two drugs and involves both the bone resorption and bone formation phenomenon of bone modeling and remodeling. Disclosure of Interest: None Declared

P103 PREVALENT FRACTURES IN WOMEN WITH PAST GLUCOCORTICOID USE ASSOCIATED WITH LOWER TRABECULAR BONE SCORE E. S. Leib1,*, R. Winzenrieth2, D. Hans3; 1Medicine, University of Vermont College of Medicine, Burlington, United States, 2Med-Imaps, Pessac, France, 3 Center Bone Disease, Lausanne University Hospital, Lausanne, Switzerland Aims: The aim of the study was to evaluate whether microarchitectural changes as measured by trabecular bone score (TBS) can identify those patients who are more likely to fracture and are on glucocorticoid (GC) therapy either presently or in the past. Methods: The study group was composed of women aged 40 and older receiving GCs (5 mg/day for 3 months). BMD was assessed at the lumbar spine (L1-L4) using a Prodigy densitometer (GE-Lunar, Madison, USA). TBS was calculated at L1-L4 using the TBS iNsightÒ (Medimaps, France). Clinical data, the presence of osteoporotic fracture (OPF), GC treatment and common clinical risk factors (CRFs) were documented. Logistic regressions (backward) were used to investigate possible relationships between independent variables and the presence of fracture for subjects presently on or with past use (p_GC) of GC. Odds ratio per standard deviation decrease (OR) was calculated. Results: The cohort consisted of 362 women treated with GCs who had TBS testing. Mean age and BMI were 62.011.2 years and 25.54.1 kg/m2. 92% were postmenopausal, 31% had a family history of osteoporosis, and 10% had a maternal history of OPF. In addition, 13% had sustained a prevalent OPF (all types) and 9% had p_GC. Correlation between TBS and BMD was, as expected, low (r50.32) and there was no correlation between TBS and BMI (r5-0.09). There were no differences in terms of age, BMI, weight and height between subjects with or without fracture (pO0.2). GC-treated patients who had sustained an OPF compared to those without OPF were characterized by a lower TBS (p50.004) while no difference in BMD was observed

Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health

Volume 17, 2014