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Recombinant parathyroid hormone (rPTH) therapy has been evaluated for skeletal repair in animal studies and clinical trials based on its known anabolic effects, but its effects on angiogenesis and fibrosis remain poorly understood. We examined the effects of rPTH therapy on blood vessel formation and osseous integration in a murine femoral allograft model, which caused a significant increase in small vessel numbers, and decreased large vessel formation (p < 0.05). Histology showed that rPTH also reduced fibrosis around the allografts to similar levels observed in live autografts, and decreased mast cells at the graft-host junction. Similar effects on vasculogenesis and fibrosis were observed in femoral allografts from Col1caPTHR transgenic mice. Gene expression profiling revealed rPTH induced angiopoietin-1 (8-fold), while decreasing angiopoietin-2 (70-fold) at day 7 of allograft healing. Finally, we demonstrate anti-angiopoietin-2 peptibody(L1-10) treatment mimics rPTH effects on angiogenesis and fibrosis. Collectively, these findings demonstrate that intermittent rPTH treatment enhances structural allograft healing by two processes: 1) anabolic effects on new bone formation via small vessel angiogenesis, and 2) inhibition of angiopoietin-2 mediated arteriogenesis. The latter effect may function as a vascular sieve to limit mast cell access to the site of tissue repair, which decreases fibrosis around and between the fractured ends of bone. Thus, rPTH therapy may be generalizable to all forms of tissue repair that suffer from limited biointegration and excessive fibrosis.

ForewordFragility fractures, low-energy injuries that occur from a fall from a standing or lower height, represent a serious public health problem. After age 50, the lifetime risk of having a fragility fracture is 33% for an American woman and 20% for a man. 1 In the United States, 2.1 million people will suffer a fragility fracture each year.1 The incidence of fragility fractures increases steeply after age 65.2 Osteoporosis is present in most patients with a fragility fracture.Hip fractures are the most serious in terms of cost and morbidity. The average cost of inpatient care for a hip fracture in 2005 was $33 962.3 The lifetime risk of having a hip fracture is 6% for men and 17.5% for women. Although the mortality risk after a hip fracture is much higher for a man, a woman's risk of dying from a hip fracture is high and exceeds the lifetime risk of death from breast cancer, uterine cancer, and ovarian cancer combined. For those who survive after a hip fracture, most do not regain their preinjury level of function, and 30% lose their independence. This loss of independence is greatly feared by patients and is very costly to patients and society.Although a hip fracture may have the most serious consequences, other bones, such as the wrist, shoulder, ankle, pelvis, and spine, frequently fracture in the osteoporotic patient. For example, the lifetime risk of a forearm or vertebral compression fracture is 16% and 15.6%, respectively, for a woman and 2.5% and 5%, respectively, for a man. 4 These statistics clearly show that fragility fractures are a major problem facing American society today, 5 and the care of such fractures presents an even greater challenge, in part because the quality of care delivered in the United States varies widely, even within one region. Many such fractures are treated in an outpatient setting, although some may be treated in the inpatient hospital setting. However, the quality of care for seniors with fragility fractures receives relatively little attention. In 2004, the United States Surgeon General issued a comprehensive report calling for health professionals to make significant improvements in our nation's bone health, and an improvement in the system and methods of care was suggested. 5There has been little written on the subject of improving the system of care delivery in the United States.The goals of this blue book are to review the methods used in inpatient and outpatient care, as well as rehabilitation of the patient with a fragility fracture. We discuss evidence-based best care models and, where evidence is lacking, present expert opinions in an effort to improve the standard and the quality of care for the patient with a fragility fracture. We hope that this monograph will provide guidance to physicians, nurses, rehabilitation therapists, other health care providers, and administrators.Stephen L. Kates, MD Editor-in-Chief Simon C. Mears, MD, PhD

Introduction: Surgical site infections (SSIs) are common complications after surgeries involving musculoskeletal tumors, but we know little about SSI risk factors unique to orthopaedic oncology. A greater understanding of these factors will help risk-stratify patients and guide surgical decision-making. Methods: A retrospective review at a single-institution identified 757 procedures done on 624 over 6 years. The patients had a preoperative diagnosis of a malignant or potentially malignant neoplasm of the bone or soft tissues. Patient-specific and procedure-specific variables and diagnosis of SSI were recorded for each case. Data were analyzed through univariate analysis and multiple logistic regression. Results: On univariate analysis, significant patient-specific risk factors for SSI included malignancy (P < 0.001), smoking history (P = 0.041), and American Society of Anesthesiologists Score (P = 0.002). Significant procedure-specific risk factors for SSI on univariate analysis included surgery time (P < 0.001), estimated blood loss (P < 0.001), blood transfusion volume (P < 0.001), neoadjuvant chemotherapy (P < 0.001), neoadjuvant radiation therapy (P < 0.001), inpatient surgery (P < 0.001), and number of previous surgeries within the study period (P < 0.001). The two factors that independently predicted risk of SSI when controlling for all other variables in a multiple logistic regression were whether the surgery was done on an inpatient basis (P = 0.005) and the number of previous surgeries done on the same site (P = 0.001). Conclusions: We found a number of risk factors that correlate markedly with SSI after orthopaedic oncology surgery. The surgeon can use these risk factors to aid in surgical decision-making.