Debora Colangelo

Teriparatide anabolic therapy as potential treatment of type II dens non-union fractures

Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type II fractures are the most common fracture pattern in elderly patients. Treatment (rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type II odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid non-union successfully treated with Teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of Teriparatide in enhancing fracture healing. Our case suggests that Teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.

Heterochronic Parabiosis Approach: is it Possible to Interrupt the Aging Process of the Intervertebral Disc Degeneration? An in vivo Experimental Study

Introduction Low back pain is a chronic health problem. It is the most common cause of limited activity. 90% of people worldwide will develop low back pain during their life. It is due, in the most cases, to the intervertebral disc degeneration (IDD). The first cause of IDD is aging. In all tissues aging is a condition characterized by mutations and genome instability, mitochondrial dysfunction, oxidative damage and consequential decline of cellular functions. Decline in tissues function is related to the loss of stem cells. These characteristics translate into different pathologies, with increasing costs for the healthcare system. In 2050 around 2 billion people worldwide will be older than 65. People are living longer but they are not healthier. Worldwide research is focused on identify the molecular pathways that can regulate expression of pro-survival networks. The purpose of this study was to determinate whether blood chimerism with a young wild type mouse (WT) could delay or reverse aging in a prematurely aging mouse model (Ercc1-/Δ). Blood chimerism was obtained by way of parabiosis, an experimental method in which two animals are surgically connected and develop a united circulation. Material and Methods 3 kinds of parabiotic pairs were generated: WT + WT at 40 days old (hisochronic parabiosis), Ercc1-/Δ + Ercc1-/Δ at 64 days old (hisochronic parabiosis) and WT + Ercc1-/Δ (heterochronic parabiosis). After surgery the couples develop anastomosis that make possible the blood chimerism. Administration of a dye (Evans blue) and fluorescent nano-beads into a single symbiont animal were used to test shared circulation in the parabiosis couples. Mice were sacrificed after 4 weeks; entire intervertebral discs were removed from the surrounding vertebral bodies by an incision along the endplate. Lumbar discs from each mouse were analyzed histologically and for nucleous polposus protein content. Expression of pro-survival networks in senescent cells and in stem cells were analyzed. Results Compared with the hisochronic controls, Ercc1-/Δ mice heterochronically paired with young WT mice had a significally improved protein content in the disc (95% CI). Histological analysis (EE & SaffO) revealed an improvement in the disc for the Ercc1-/Δ individual in the heterochronic pair relative to the hisochronic ones. We observed a reactivation of stem cells when exposed to younger serum and a migration of young stem cells to the old mice (using GFP protein expressed in the younger mouse). Furthermore µCT highlighted an improvement of the bone quality. Conclusion These results indicate that spine of the progeroid mice were rejuvenated in the older mice when exposed to a serum derived from younger organism. Senescent cells secrete pro-inflammatory cytokines, and chemokines, which together constitute the senescence-associated secretory phenotype. We believe that stem cells are quiescent in old organism and that the environment can reactivate them. Moreover this factor can attract young stem cells from the young mice. The factor responsible for this, this elixir of youthful, although currently unidentified, could potentially be used as an effective treatment to rescue IDD as well other pathologies connected to aging.

Kyphoplasty versus Conservative Treatment: A Case–Control Study in 110 Postmenopausal Women Population. Is Kyphoplasty Better than Conservative Treatment?

Introduction Osteoporosis is a highly prevalent and one of the most debilitating and costly chronic diseases worldwide and it is also responsible for approximately 1.5 million vertebral fragility fractures (VCFs) a year.1,2,3 Most of the patients experiencing an osteoporotic VCFs remain asymptomatic or minimally symptomatic; however, a large part of these patients do experience significant pain, resulting in decreased quality of life and disability and mortality too.4 The consequences of these fractures include pain and, in many cases, progressive vertebral collapse with resultant spinal kyphosis. Minimally invasive procedures, namely, kyphoplasty and vertebroplasty, represent a recent advance to the treatment of osteoporotic VCFs.5,6,7 The aim of this study is to compare effects in terms of recovery and quality of life and to compare deformity prevention efficacy of kyphoplasty and conservative treatment in postmenopausal women with an osteoporotic VCF. The aim of this study is to provide an efficacy assessment of kyphoplasty as compared with standard conservative treatment in postmenopausal women (bracing immobilization).8,9,10 Patients and Methods We designed a retrospective case–control study on 110 postmenopausal women. Included in this study were patients who were diagnosed with postmenopausal osteoporosis according to National Osteoporosis Foundation (NOF) guidelines, with a recent (< 2 weeks) symptomatic osteoporotic vertebral compression fracture (VCF), no more than two (if any) old VCFs with no resultant kyphotic deformity, and whose treatment starts no later than 15 days from the VCF time. Study population was split in a surgery cohort and a conservative cohort according to the provided treatment. All patients were asked to fill in VAS, SF-12, and Eq. 5D questionnaires at different time points up to 12 months after treatment. Segmental kyphosis at fracture level was also measured for our analysis. Results Kyphoplasty-treated patients had lower back pain VAS scores at 1 month as compared with conservatively treated patients (p < 0.05). Eq. 5D questionnaire also showed a better quality of life at 1 month for surgically treated patients (p < 0.05). As for the SF-12 no significant difference was observed. At 12 months, scores from all scales were not statistically different between the two cohorts, although surgically treated patients showed better trends than conservatively treated patients in pain and quality of life. Kyphoplasty was able to restore more than 55% of the original segmental kyphosis, whereas patients in conservative cohort lost 6.67% of the original segmental kyphosis on average. Conclusion Kyphoplasty seems to be a safe and effective procedure in reducing back pain due to painful VCF. The kyphosis restoring effect is also extremely interesting and can be achieved only in the first days after fracture time. In conclusion, kyphoplasty is a procedure that offers a fast recovery and a better quality of life at 1 month after treatment, helping restoring segmental kyphosis after VCFs.11,12,13 Acknowledgments There was no external funding source and no funding source played a role in the investigation. References Who are candidates for prevention and treatment for osteoporosis? Osteoporos Int 1997;7(1):1–6 Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17(12):1726–1733 Iqbal MM, Sobhan T. Osteoporosis: a review. Mo Med 2002;99(1):19–24 Gold DT. The clinical impact of vertebral fractures: quality of life in women with osteoporosis. Bone 1996;18(3, Suppl):185S–189S Jarvik JG, Kallmes DF. Point of view. Efficacy of vertebroplasty and kyphoplasty. Spine 2009;34(6):613–614 Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009;361(6):569–579 Weinstein JN. Balancing science and informed choice in decisions about vertebroplasty. N Engl J Med 2009;361(6):619–621 Lyritis GP, Mayasis B, Tsakalakos N, et al. The natural history of the osteoporotic vertebral fracture. Clin Rheumatol 1989;8(2, Suppl 2):66–69 Prather H, Watson JO, Gilula LA. Nonoperative management of osteoporotic vertebral compression fractures. Injury 2007;38(3, Suppl 3):S40–S48 Garfin SR, Yuan HA, Reiley MA. New technologies in spine: kyphoplasty and vertebroplasty for the treatment of painful osteoporotic compression fractures. Spine 2001;26(14):1511–1515 Ledlie JT, Renfro M. Balloon kyphoplasty: one-year outcomes in vertebral body height restoration, chronic pain, and activity levels. J Neurosurg 2003;98(1, Suppl):36–42 Voggenreiter G. Balloon kyphoplasty is effective in deformity correction of osteoporotic vertebral compression fractures. Spine 2005;30(24):2806–2812 Pradhan BB, Bae HW, Kropf MA, Patel VV, Delamarter RB. Kyphoplasty reduction of osteoporotic vertebral compression fractures: correction of local kyphosis versus overall sagittal alignment. Spine 2006;31(4):435–441