Introduction: Osteoporosis is a disease characterized by a low bone mass and the development of nontraumatic fractures. Approximately 700,000 elderly women in the US are newly diagnosed with osteoporotic vertebral fractures every year. Noninvasive measurements of bone mineral density (BMD) are central to the diagnosis and management of osteoporosis. However, BMD alone is not completely satisfactory in vertebral fracture risk assessment. The aim of this study was to identify clinical and laboratoristic factors associated with an increased risk of vertebral fractures in osteoporotic Caucasian women and to define a new clinically relevant scale of risk.

Methods: 475 patients consecutively admitted at our ambulatory for the treatment of vertebral osteoporosis were included in the study. All patients were affected by post-menopausal osteoporosis according to the WHO classification criteria. Exclusion criteria were major infectious diseases, tumors and major diseases of sense organs. We attempted to determine whether parameters such as age, body mass index, smoking and alcohol habitudes, femoral and lumbar T-scores, femoral and lumbar Z-scores, femoral and lumbar BMD, total and bone alkaline phosphatase and L3 and T7 vertebral volumes were associated with the risk of vertebral fractures.

Results: 173 patients of the entire population presented at least one vertebral fracture for a total of 488 fractures (238 thoracic and 250 lumbar collapses). When considered alone, age (> 65 years-p=0,0001), lumbar T-score (≤-3,5-p=0,0001), lumbar Z-score (≤-2,5-p=0,0050), lumbar BMD (≤0,800-p=0,0017), femoral T-score (≤-3,5-p=0,0090), femoral Z-score (≤-2,5-p=0,0127), L3 volume (≤-2,0SD–p=0,0023) and T7 volume (≤-2,0SD–p=0,0075) were significantly associated with an increased risk of vertebral fractures. Considering only the patients with two fractures or more, the same parameters with the exception of the femoral T-score resulted strongly associated with the risk of new vertebral fractures. Moreover, there was a significantly increased risk of vertebral fractures when two or more of these parameters were present together (p = 0.02). On the base of the obtained data we have then defined a new scale of risk (from grade I-low risk to grade IV-very high risk-p=0.0123) confirmed in a prospective study conducted on 71 osteoporotic patients followed for 30 months.

Conclusion: We propose a new clinical scale to easily identify the osteoporotic patient at risk of new vertebral fractures.

Aims: As inflammation plays a key role in the etiology of intervertebral disc degeneration, we suggest a possible contribution of pro-inflammatory gene polymorphisms in the pathogenesis of adolescent idiopathic scoliosis (AIS). The nucleus pulposus of scoliotic discs responds to exogenous stimuli by secreting interleukin-6 (IL-6) and other inflammatory cytokines. The association between matrix metalloproteinases (MMPs) and disc degeneration has been reported by several investigators. A human MMP-3 promoter 5A/6A gene polymorphism regulates MMP-3 genes expression, while the G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein.

Methods: We conducted a case-control study to investigate whether the 5A/6A polymorphism of the MMP-3 gene and the G/C polymorphism of the promoter region of IL-6 gene were associated with susceptibility to AIS.

Results: The frequency of the 5A/5A genotype of MMP-3 gene polymorphism in patients with scoliosis was almost 3 times higher than in controls (30.2 % vs 11.2 %, p 0.001) and the frequency of the G/G genotype of IL-6 gene polymorphism in patients with scoliosis was almost 2 times higher than in controls (52.8 % vs 26.2 %, p < 0.001). 5A/5A genotype of MMP-3 gene polymorphism and G/G genotype of IL-6 gene polymorphism are independently associated with an higher risk of scoliosis (odds ratio respectively 3.34 and 10.54).

Conclusions: This is the first study that has evaluated the possibility that gene variants of IL-6 and MMPs might be associated with scoliosis and suggests that MMP-3 and IL-6 promoter polymorphisms constitute important factors for the genetic predisposition to scoliosis.