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A previous fracture may be a misleading fracture risk factor
Abstracts / Bone 47 (2010) S29–S52
VitD levels (95% CI 62.6–70.2) than non-supplemented subjects (N = 415, 32.6–39.2), with identical seasonal variation. Summer 2008 (sunniest season) had the highest VitD averages, 71.5–87.3 in the supplemented (N = 69) and 36.1–48.0 in the non-supplemented (N = 73). In winter 2007, mean levels for supplemented (N = 34) were 54.6–73.0 versus 20.1–34.7 for non-supplemented (N = 62). Discussion: VitD supplementation raised serum VitD levels significantly, about 30 units on average. Only those taking supplements during the sunniest season got close to a normal level (≥80). Nonsupplemented people were insufficient all year round, and close to deficiency in winter. There is a case for universal, seasonally-adjusted VitD supplementation. Image / Graph:
S31
Aff4). For males 27% in Aff1 had 3 or more fractures compared to 3% in Aff4. On the other hand, the patients with a late in life first fracture tended to have a larger percentage of femoral and vertebral fractures. 3% in Aff1 suffered a femoral fracture compared to 13% in Aff4. For vertebral fractures the respective vales were 8% and 22%. For males the vales were 7% and 15% for femoral fractures and 23% and 48% for vertebral fractures. Approximately 10% of patients having suffered forearm fractures or other fractures reported lasting sequels from the fractures. For femoral and vertebral fractures the same values were 30%. Having had a fracture has been reported to substantially increase the risk for new fractures. The present results comply with these findings in the respect that an early fracture is a risk for having several life time fractures. However, among those with a later in life first fracture there was a larger proportion of patients having fractures with serious sequels. Although an early fracture may indicate a risk of new fractures, patients with a late in life first fracture may have a high risk of serious fractures. Considering patients without a fracture history as low risk patients may not be advisable. Disclosure of Interest: None declared. Keywords: fracture inicidence doi:10.1016/j.bone.2010.04.049
OC07 Bone marrow stromal cells and adiponectin contribute to myeloma pathogenesis in vivo J.A. Fowler1, G.R. Mundy1, S.T. Lwin1, J.R. Edwards⁎1, C.M. Edwards1 1 Vanderbilt Center for Bone Biology, Vanderbilt University, Nashville, United States Disclosure of Interest: None declared. Keywords: older people, seasonal variation, vitamin D doi:10.1016/j.bone.2010.04.048
OC06/AHP06 A previous fracture may be a misleading fracture risk factor A. Hoiseth⁎1 1 Curato Rtg., Oslo, Norway A previous fracture is commonly assumed to be a risk factor for having further life time fractures. The purpose of this paper was to describe the number and type of fractures occurring in patients depending on age at first fracture. A total of 9135 patients referred routine measurement of bone mass were included in the study. 3351 reported having had at least one fracture. Fractures were recorded as fore-arm fractures, vertebral fractures, femoral fractures and as other fractures. The material was divided into 4 age-at-firs-fracture groups. First fracture before age 30 (Aff1). First fracture at age 31 to 50 (Aff2). First fracture at age 51 to 65 (Aff3). First fracture after age 65 (Aff4). The patients also recorded clinical and social consequences of the fractures. The occurrence of fractures showed a peak age 10 to 15, then a slow increase after age 25 and with a substantial increase after age 50. Age at first fracture showed a similar dispersion. Patients with an early in life first fracture had a larger number of fractures that those with a later in life first fracture. In Aff1 24% had 3 or more fractures compared to 12% in Aff4. Aff1 also had the largest percentage of 2 fractures (29% compared to 24% in
The bone marrow (BM) microenvironment is known to play a critical role in tumor growth and the development of myeloma (MM) bone disease, however its role in the initial establishment of MM is unknown. To investigate this in vivo, we have utilized the well-characterized Radl model of MM in which MM is propagated by inoculation of 5TMM cells into C57Bl/KalwRij (KalwRij) mice. Since MM grows in KaLwRij mice, but not in closely related C57Bl6 mice, this suggests the KaLwRij BM creates a unique and permissive milieu for MM. In support of this, we have found that co-inoculation of 5TGM1 MM cells with a bone marrow stromal cell (BMSC) line isolated from MM-bearing KaLwRij mice can promote MM establishment and development of osteolytic bone disease in C57Bl6 mice, enabling, for the first time, MM development in a non-permissive microenvironment in vivo. To identify factors that were differentially expressed in the KalwRij BM microenvironment we performed microarray analysis on BM of age-matched non-permissive C57Bl6 and MM-permissive KalwRij mice. Adiponectin (ADPN) was decreased in KalwRij BM as compared with C57Bl6 BM and we confirmed a 68.3% decrease in ADPN expression in the KalwRij BM and 30.8% decrease in serum concentrations of ADPN in KalwRij mice as compared with C57Bl6 mice. Normal BM-derived stroma, including osteoblasts and fibroblasts, were found to express both ADPN and its receptors, however BMSCs from MM-permissive KaLwRij mice did not express ADPN. 5TGM1 MM cells did not express ADPN but did express ADPN receptors. We investigated the anti-MM effects of ADPN both in vitro and in vivo. 5TGM1 MM cells were treated with recombinant ADPN for 72 hours. Adiponectin induced over 30% reduction in proliferation and over 130% increase in apoptosis. To test the direct anti-MM effects of ADPN in vivo, we used an apolipoprotein mimetic, L-4F, which has been previously shown to increase serum ADPN levels. KalwRij mice were inoculated
VitD levels (95% CI 62.6–70.2) than non-supplemented subjects (N = 415, 32.6–39.2), with identical seasonal variation. Summer 2008 (sunniest season) had the highest VitD averages, 71.5–87.3 in the supplemented (N = 69) and 36.1–48.0 in the non-supplemented (N = 73). In winter 2007, mean levels for supplemented (N = 34) were 54.6–73.0 versus 20.1–34.7 for non-supplemented (N = 62). Discussion: VitD supplementation raised serum VitD levels significantly, about 30 units on average. Only those taking supplements during the sunniest season got close to a normal level (≥80). Nonsupplemented people were insufficient all year round, and close to deficiency in winter. There is a case for universal, seasonally-adjusted VitD supplementation. Image / Graph:
S31
Aff4). For males 27% in Aff1 had 3 or more fractures compared to 3% in Aff4. On the other hand, the patients with a late in life first fracture tended to have a larger percentage of femoral and vertebral fractures. 3% in Aff1 suffered a femoral fracture compared to 13% in Aff4. For vertebral fractures the respective vales were 8% and 22%. For males the vales were 7% and 15% for femoral fractures and 23% and 48% for vertebral fractures. Approximately 10% of patients having suffered forearm fractures or other fractures reported lasting sequels from the fractures. For femoral and vertebral fractures the same values were 30%. Having had a fracture has been reported to substantially increase the risk for new fractures. The present results comply with these findings in the respect that an early fracture is a risk for having several life time fractures. However, among those with a later in life first fracture there was a larger proportion of patients having fractures with serious sequels. Although an early fracture may indicate a risk of new fractures, patients with a late in life first fracture may have a high risk of serious fractures. Considering patients without a fracture history as low risk patients may not be advisable. Disclosure of Interest: None declared. Keywords: fracture inicidence doi:10.1016/j.bone.2010.04.049
OC07 Bone marrow stromal cells and adiponectin contribute to myeloma pathogenesis in vivo J.A. Fowler1, G.R. Mundy1, S.T. Lwin1, J.R. Edwards⁎1, C.M. Edwards1 1 Vanderbilt Center for Bone Biology, Vanderbilt University, Nashville, United States Disclosure of Interest: None declared. Keywords: older people, seasonal variation, vitamin D doi:10.1016/j.bone.2010.04.048
OC06/AHP06 A previous fracture may be a misleading fracture risk factor A. Hoiseth⁎1 1 Curato Rtg., Oslo, Norway A previous fracture is commonly assumed to be a risk factor for having further life time fractures. The purpose of this paper was to describe the number and type of fractures occurring in patients depending on age at first fracture. A total of 9135 patients referred routine measurement of bone mass were included in the study. 3351 reported having had at least one fracture. Fractures were recorded as fore-arm fractures, vertebral fractures, femoral fractures and as other fractures. The material was divided into 4 age-at-firs-fracture groups. First fracture before age 30 (Aff1). First fracture at age 31 to 50 (Aff2). First fracture at age 51 to 65 (Aff3). First fracture after age 65 (Aff4). The patients also recorded clinical and social consequences of the fractures. The occurrence of fractures showed a peak age 10 to 15, then a slow increase after age 25 and with a substantial increase after age 50. Age at first fracture showed a similar dispersion. Patients with an early in life first fracture had a larger number of fractures that those with a later in life first fracture. In Aff1 24% had 3 or more fractures compared to 12% in Aff4. Aff1 also had the largest percentage of 2 fractures (29% compared to 24% in
The bone marrow (BM) microenvironment is known to play a critical role in tumor growth and the development of myeloma (MM) bone disease, however its role in the initial establishment of MM is unknown. To investigate this in vivo, we have utilized the well-characterized Radl model of MM in which MM is propagated by inoculation of 5TMM cells into C57Bl/KalwRij (KalwRij) mice. Since MM grows in KaLwRij mice, but not in closely related C57Bl6 mice, this suggests the KaLwRij BM creates a unique and permissive milieu for MM. In support of this, we have found that co-inoculation of 5TGM1 MM cells with a bone marrow stromal cell (BMSC) line isolated from MM-bearing KaLwRij mice can promote MM establishment and development of osteolytic bone disease in C57Bl6 mice, enabling, for the first time, MM development in a non-permissive microenvironment in vivo. To identify factors that were differentially expressed in the KalwRij BM microenvironment we performed microarray analysis on BM of age-matched non-permissive C57Bl6 and MM-permissive KalwRij mice. Adiponectin (ADPN) was decreased in KalwRij BM as compared with C57Bl6 BM and we confirmed a 68.3% decrease in ADPN expression in the KalwRij BM and 30.8% decrease in serum concentrations of ADPN in KalwRij mice as compared with C57Bl6 mice. Normal BM-derived stroma, including osteoblasts and fibroblasts, were found to express both ADPN and its receptors, however BMSCs from MM-permissive KaLwRij mice did not express ADPN. 5TGM1 MM cells did not express ADPN but did express ADPN receptors. We investigated the anti-MM effects of ADPN both in vitro and in vivo. 5TGM1 MM cells were treated with recombinant ADPN for 72 hours. Adiponectin induced over 30% reduction in proliferation and over 130% increase in apoptosis. To test the direct anti-MM effects of ADPN in vivo, we used an apolipoprotein mimetic, L-4F, which has been previously shown to increase serum ADPN levels. KalwRij mice were inoculated