Low-grade inflammation negatively affects bone. Resveratrol is a natural compound proven to possess both anti-inflammatory and bone protective properties. However, it is uncertain if the bone effects are mediated though anti-inflammatory effects. Firstly, we investigated if resveratrol affects proliferation and differentiation of human bone marrow-derived mesenchymal stem cells. Secondly, we investigated if inflammation negatively affects proliferation and differentiation, and if resveratrol counteracts this through anti-inflammatory effects. Mesenchymal stem cells were obtained from bone marrow aspiration in 13 healthy individuals and cultured towards the osteoblast cell lineage. The cells were stimulated with resveratrol, lipopolysaccharide (LPS), LPS + resveratrol, or vehicle (control) for 21 days. Compared to control, resveratrol decreased cell number by 35 % (p < 0.05) and induced differentiation (a 3-fold increase in alkaline phosphatase (p < 0.002), while P1NP and OPG showed similar trends). LPS induced inflammation with a 44-fold increase in interleukin-6 (p < 0.05) and an extremely prominent increase in interleukin-8 production (p < 0.05) relative to control. In addition, LPS increased cell count (p < 0.05) and decreased differentiation (a reduction in P1NP production (p < 0.02)). Co-stimulation with LPS + resveratrol did not reduce interleukin-6 or interleukin-8, but nonetheless, cell count was reduced (p < 0.05) and alkaline phosphatase, P1NP, and OPG increased (p < 0.05 for all). Thus, resveratrol stimulates osteoblast differentiation independently of inflammation.

57 patients who underwent surgery for slipped lumbar disc for the first time were examined prospectively 6 months after surgery for the purpose of deciding the correlation between the outcome of surgery and social and psychological factors. The following factors were found to be of importance: Female sex, action for damages, prolonged disease of the back; prolonged, current attack, report of long-term illness, pathological pain producing, anxiety, depression and multiple somatic complaints revealed by Minnesota Multiple Personality Inventory (MMPI), severe pain reported immediately post-operatively, employment and the presence of complete herniation at surgery. A closer study revealed 3 factors which were important independently and which explained the other factors: Admission of symptom scale (Ad) in the MMPI, the duration of the current attack and whether the patient was employed. On this basis we define a group with severe psychological and social strain (PASS), 57% of which had a poor outcome. 5% of the rest of the patients had a poor outcome. With the pre-operative assessment of whether or not the patients are under severe psychological and social strain, the outcome of surgery could be predicted correctly in 86% of the patients.

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57 patients who were operated upon for the first time for slipped lumbar disk have been investigated in a prospective blind follow-up design. In both the preoperative and postoperative evaluation objective as well as subjective conditions have been considered, and the surgeons have not re-examined the patients. There is a 100% follow-up of the patients. We found that the following preoperative conditions are associated with surgical outcome, 6 and 24 months postoperatively: Medical parameters like statement of pain and surgical findings; social parameters such as being employed, duration of education, and whether you get sufficient social support from family and friends; duration of sick-leave, actions for damages, and number of life events. Psychological parameters such as pain drawing and the MMPI-scales: F, K, Hs, D, Hy, Pa, Pt, Sc, Ma, and Ad. In the statistical analysis multiple linear regression analysis is used, which allows evaluation of the different parameters compared with each other. It is found that conditions such as being employed, increase of the MMPI-scale Ad, alone could explain the 42% difference in surgical outcome. Good outcome is correctly predicted in 88% of the cases with observed good outcome. Poor outcome is correctly predicted in 54% of the cases with observed poor outcome.

Increasing age is associated with reduced bone mineral content and increased risk of fractures. This is caused by a relative insufficiency of osteoblasts compared with osteoclasts. We therefore wanted to examine the potential differences in proliferation, differentiation, and expression of cytokines between human osteoblasts (hOBs) obtained from young and elderly individuals. Cultures of hOBs were obtained from 11 elderly (73-85 years) and 15 young (21-27 years) healthy individuals. The cells were stimulated with hGH, IGF-I, hGH + IGF-I, and TGF-β1. Proliferation was evaluated by thymidine incorporation, and differentiation was evaluated by alkaline phosphatase, OPG, and PINP production. Expression of IL-6, TGF-β1, OPG, and RANKL was investigated using real-time PCR and three carefully selected housekeeping genes. Combined stimulation with hGH and IGF-I increased proliferation without differences between hOBs obtained from young and elderly individuals. hOBs from young individuals responded to stimulation with vitamin D with a more pronounced increase in alkaline phosphatase: 107 ± 17% vs. 43 ± 5%, P < 0.01. Stimulation with TGF-β1 decreased OPG production by hOBs from elderly individuals but not from young individuals, P < 0.05. hOBs from elderly individuals expressed significantly higher amounts of IL-6 mRNA (P < 0.05) and less OPG and TGF-β1 mRNA (P = 0.08 and P = 0.08, respectively) compared with hOBs from young individuals. In conclusion, hOBs from elderly individuals express more IL-6 mRNA and less OPG and TGF-β1 mRNA than hOBs from young individuals. This could partly explain the reduced bone mass and increased fracture risk seen in the elderly. hOBs from young and elderly individuals responded similarly to short-term stimulation of proliferation and differentiation.