A32 Low bone mass in premenopausal women with major depression. For the power study group Giovanni Cizza NIDDK, National Institutes of Health, Bethesda, MD, USA Aims/Objectives: An increased prevalence of low bone mineral density (BMD) has been reported in patients with major depression (MDD), mostly women. Our goal was to investigate the association of MDD and BMD [1]. Methods: We report baseline BMD measurements in 89 preme- nopausal women with MDD and 44 healthy control women enrolled in a prospective study of bone turn-over. The BMD was measured by DXA at the spine, hip, and forearm. Mean hourly levels of plasma 24-h cytokines, 24-h urinary free cortisol and catecholamine excretion were also measured. MDD was defined according to the DSM-IV. Results: The prevalence of low BMD, defined as a T-score of less than -1, was greater in women with MDD vs. controls at femoral neck (17% vs. 2%, P =.02) and total hip (15% vs. 2% P = .02), and tended to be greater at the lumbar spine (20% vs. 9%; P = 0.14). BMD, expressed as g/cm2, was lower in women with MDD at the femoral neck (0.849 ± 0.121 vs. 0.866 ± 0.094, P = .05) and at the lumbar spine (1.024 ± 0.117 vs.1.043 ± 0.092, P =.05) and tended to be lower at the radius (0.696 ± 0.049 vs. 0.710 ± 0.055; P =.07). Women with MDD had increased pro-inflammatory and decreased anti-inflammatory cytokines. Conclusions: Low BMD is more prevalent in premenopausal women with MDD. The BMD deficits are of clinical significance, and comparable in magnitude to those resulting from established risk factors for osteoporosis, such as smoking and reduced calcium intake. The possible contribution of immune/inflammatory imbalance to low BMD in premenopausal women with MDD remains to be clarified. Reference: [1] Eskandari F, Martinez PE, Torvik S, Phillips TM, Sternberg EM, Mistry S, Ronsaville D, Wesley R, Toomey C, Sebring NG, Reynolds JC, Blackman MR, Calis KA, Gold PW, Cizza G; for the Premenopausal, Osteoporosis Women, Alendronate, Depression (POWER) Study Group. doi:10.1016/j.bone.2008.08.034 A33 Age-related changes in the osteogenic differentiation potential of BMSC Weixi Zhang, Mark Hamrick, Carlos Isales, Xing-Ming Shi Medical College of Georgia, Augusta, GA 30912, USA Age-dependent bone loss has been well-documented in both human and animal models. Although the underlying causal mechan- ism(s) are probably multifactorial, it has been hypothesized that alterations in progenitor cell number or function are important. Little is known regarding the properties of bone marrow stromal cells (BMSCs) or bone progenitor cells during the aging process so the question of whether aging alters BMSC/progenitor osteogenic differ- entiation remains unanswered. In the present study, we examined age- dependent changes in bone marrow progenitor cell number and differentiation potential among mature (3- and 6-month-old), mid- dleaged (12- and 18-month-old), or aged (24-month-old) C57BL/6 mice. Bone marrow stromal cells (BMSCs) or progenitors were isolated from five-age groups of C57BL/6 mice using negative-immuno-depletion and positive-immuno-selection approaches. The osteogenic differentiation potential of multi-potent BMSCs was determined using standard osteogenic differentiation procedures. Our results demonstrate that both BMSC/progenitor number and differentiation potential increase between the ages of 3 and 18 months, and decrease rapidly thereafter with advancing age. These results are consistent with the changes of the mRNA levels of osteoblast lineage-associated genes. Our data suggest that the decline in BMSC number and osteogenic differentiation capacity are important factors contributing to age-related bone loss. doi:10.1016/j.bone.2008.08.035 A34 Osteoclastogenic cytokines - NF-κB signaling in methotrexate chemotherapy-induced osteoporosis Tristan King 1 , Michaela Scherer 2 , Jo Cool 2 , Jiake Xu 3 , Bruce Foster 2 , Cory Xian 4 1 University of Adelaide, Adelaide, Australia 2 Women's and Children's Hospital, Adelaide, Australia 3 University of Western Australia, Perth, Australia 4 University of South Australia, Adelaide, Australia Chemotherapy is known to cause many adverse effects one of which manifests as osteoporosis in bone; however the mechanisms behind decreased bone mineral density induced by chemotherapy regimens are poorly understood. Utilising a methotrexate chemother- apy model in rats, we have demonstrated potential roles for the osteoclasts and the NF-κB signaling pathway in chemotherapy induced osteoporosis. Male, 7 week-old Sprague Dawley rats received daily methotrexate injections (0.75 mg/kg) for five consecutive days. Bone and marrow samples were collected at various days post the initial injection (days 4, 6, 9, 14 and 21). Histological analysis indicated increased osteoclast density on trabecular bone in tibia on day 9, in accordance with the increased numbers of TRAP + osteoclasts grown ex vivo from marrow collected from day 9 rats. Real time RT-PCR analysis showed an increase in the expression of IL-1, IL-6, TNF-α and RANKL in day 9 bone samples. The nuclear transcriptor NF-κB is known to be activated by these osteoclastogenic cytokines and once activated is a mediator of osteoclast formation, activity and survival. Here, a luciferase assay with RAW cells stably transfected with the NF-κB construct revealed that serum collected from day 6 methotrexate treated-rats potentiated the activation of NF-κB. Consistently we also demonstrated that serum collected from methotrexate treated rats induced the formation of mature TRAP + osteoclasts from normal marrow cells without the addition of exogenous osteoclastogenic factors. We propose that the increased osteoclast formation, increased osteoclastogenic cytokine gene expression and coupled NF-κB activa- tion could contribute to methotrexate chemotherapy-induced imbal- ance in bone turnover homeostasis favoring osteoclast number and activity and resulting in osteoporosis. doi:10.1016/j.bone.2008.08.036 A35 Decay in jumping exercise-induced tibial gains in female rats is not uniform Foong Kiew Ooi 1 , Rabindarjeet Singh 1 , Harbindar Jeet Singh 2 , Yoshihisa Umemura 3 , Seigo Nagasawa 3 1 Sports Science Unit, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia 2 Faculty of Medicine, Universiti Technologi MARA, Shah Alam, Selangor, Malaysia 3 School of Health and Sports Science, Chukyo University, Toyota, Japan S50 ABSTRACTS / Bone 43 (2008) S38–S75