Konstantin Horas

Risk factors for pelvic insufficiency fractures and outcome after conservative therapy

PURPOSE The prevalence of osteoporosis has continuously increased over the past decades and it is set to increase substantially as life expectancy rises steadily. Fragility or osteoporotic fractures of the pelvis often occur after low energy falls e.g. from standing, however, some patients present with assumed insufficiency fractures of the pelvis without a previous trauma. Osteoporotic fractures impose a tremendous economic burden and these fractures deserve attention as they lead to a decrease in mobility with an increase in dependency and are associated with a high rate of mortality. To date, little is known about potential risk factors for pelvic insufficiency fractures. Furthermore, information on clinical outcome is scarce. In view of this rather limited knowledge, we aimed to identify potential risk factors for pelvic insufficiency fractures and to collect information on their short- and long-term outcomes. METHODS Files of all consecutive patients admitted between January 2010 and December 2013 for a pelvic insufficiency fracture were enrolled in this study. Pelvic fractures that occurred on tumorous bone or after high-energy trauma were excluded. Fractures of the pelvis included all pelvic bones except the coccyx. For all patients, we recorded clinical and biological parameters available from their medical history. For comparison, the same biological and clinical parameters were evaluated in an age matched control group of 1083 patients aged over 70 who were admitted to our orthopaedic department to undergo knee or hip arthroplasty. The statistical analyses used or Fisher test for percentages comparison, 2-tailed t-tests and Mann Whitney for mean comparison. To determine what factors are predictors and what factors are confounders of pelvic insufficiency fractures, multivariate linear regression analysis using the fracture as a continuous variable was performed. RESULTS Ninety-three patients with a pelvic insufficiency fracture were identified. Following the Rommens and Hofmann classification for fragility fractures of the pelvis (FFP), 51 were FFP Type Ia, 26 were FFP Type IIb lesions and 26 were FFP Type IIc. Osteoporosis was found to be significantly associated with pelvic insufficiency fractures (p=0.003), as was hypertension (p=0.036), diabetes (p=0.021), vitamin D deficiency (p=0.004), hypocalcaemia (p=0.002) and nicotine abuse (p=0.0012) after adjustment for possible confounders in the multivariate linear regression analysis. Comparing the autonomous state before and after pelvic fracture, a high loss of autonomy was observed. Patients needing daily assistance nearly doubled their number. Overall mortality was high (20%). CONCLUSIONS In conclusion, this study showed multiple risk factors for pelvic insufficiency fractures. Some, like vitamin D deficiency, can benefit easy preventive measures. Outcome of conservative therapy is poor, with loss of social and physical independence and autonomy. The mortality rate is high. Efforts should be made in preventing pelvic insufficiency fractures. All patients should be treated for the severe osteoporosis being associated with these fracture type.

Animal Models for Breast Cancer Metastasis to Bone: Opportunities and Limitations

Skeletal metastases occur frequently in patients with breast cancer and are associated with significant morbidity and poor survival. Numerous animal models have been developed to investigate the biology of bone metastases and effective preventative or therapeutic approaches. However, no single animal model recapitulates the complexity of the metastatic process in toto. Therefore, selection of the animal model most appropriate for the question under investigation is crucial for the validity of the experimental outcome. This review provides an overview of the currently available animal models for breast cancer metastasis to bone with an emphasis on innovative xenograft models and imaging technologies.

Loss of the vitamin D receptor in human breast and prostate cancers strongly induces cell apoptosis through downregulation of Wnt/β-catenin signaling

Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25(OH)2D] are mediated through binding to the vitamin D receptor (VDR). Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad (MDA-MB-231), subcutaneously (PC3) or intra-tibially (both cell lines) in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls. These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/β-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1, interleukin-6 (IL-6), and IL-8. Stabilization of β-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer.

The role of soft-tissue traction forces in bone segment transport for callus distraction A force measurement cadaver study on eight human femora using a novel intramedullary callus distraction system

Abstract Callus distraction using bone segment transport systems is an applied process in the treatment of bone defects. However, complications such as muscle contractures, axial deviation and pin track infections occur in the treatment process using the currently available devices. Since successful treatment is influenced by the applied distraction force, knowledge of the biomechanical properties of the involved soft tissues is essential to improve clinical outcome and treatment strategies. To date, little data on distraction forces and the role of soft-tissue traction forces are available. The aim of this study was to assess traction forces generated by soft tissues during bone segment transport using a novel intramedullary callus distraction system on eight human femora. For traction force measurements, bone segment transport over 60-mm femoral defects was conducted under constant load measurement using 40- and 60-mm bone segments. The required traction forces for 60-mm bone segments were higher than forces for 40-mm bone segments. This study demonstrates that soft tissues are of relevance biomechanically in bone segment transport. The size of the bone segment and the selection of the region for osteotomy are of utmost importance in defining the treatment procedure.

A novel intramedullary callus distraction system for the treatment of femoral bone defects

An intramedullary device has some advantages over external fixation in callus distraction for bone defect reconstruction. There are difficulties controlling motorized intramedullary devices and monitoring the distraction rate which may lead to poor results. The aim of this study was to design a fully implantable and non-motorized simple distraction nail for the treatment of bone defects. The fully implantable device comprises a tube-in-tube system and a wire pulling mechanism for callus distraction. For the treatment of femoral bone defects, a traction wire, attached to the device at one end, is fixed to the tibial tubercle at its other end. Flexion of the knee joint over a predetermined angle generates a traction force on the wire triggering bone segment transport. This callus distraction system was implanted into the femur of four human cadavers (total 8 femora), and bone segment transport was conducted over 60-mm defects with radiographic monitoring. All bone segments were transported reliably to the docking site. From these preliminary results, we conclude that this callus distraction system offers an alternative to the current intramedullary systems for the treatment of bone defects.

Vitamin D and the Elderly Orthopedic Patient

Abstract Vitamin D is a key player in calcium homeostasis and bone health. Beyond these well-known effects, new data suggest that vitamin D deficiency potentiates a variety of chronic disease states, including diabetes, cancer, and depression. Extremely low vitamin D levels have been associated with osteomalacia and impaired muscle function, both core elements in the field of orthopedic surgery. Good muscle function and healthy bones are essential for fast rehabilitation and positive outcome after orthopedic surgery as well, especially for elderly patients seeking good physical function. Physical function is important for the preservation of independence in daily life and for the prevention of falls, which are associated with fractures and high mortality. This review focuses on the role of vitamin D deficiency in elderly orthopedic patients.

Vitamin D Deficiency: The Missing Etiological Factor in the Development of Juvenile Osteochondrosis Dissecans?

Background: Vitamin D deficiency can result in rickets and hypocalcemia during infant and childhood growth. There is an increasing interest in the role of vitamin D with regards to childhood bone health. Osteochondrosis dissecans (OD) is a common disease affecting different joints. To date, the exact etiology of OD still remains unclear. The aim of this study was to evaluate a possible association of vitamin D deficiency and juvenile OD. Methods: A retrospective chart review of the years 2010 to 2015 of all orthopaedic patients with an initial diagnosis of juvenile OD admitted to undergo operative treatment of the OD was performed. Patient demographics, medical history, information on sports activity (if available) and serum vitamin D (25-OH-D) level on admission date were obtained. For statistical comparison, we measured baseline prevalence of vitamin D insufficiency in age-matched orthopaedic patients presenting at the department of pediatric orthopaedics. Results: A total of 80 patients were included in this study. Overall, 97.5% (n=78) of tested patients in the OD group had serum vitamin D levels below the recommended threshold of 30 ng/mL (mean value of 10.1 ng/mL (±6.7 ng/mL)). Over 60% (n=49) were vitamin D deficient, 29 patients (37%) showed serum levels below 10 ng/mL corresponding to a severe vitamin D deficiency. Of note, only 2 patients (2.5%) reached serum vitamin D levels above the recommended threshold of 30 ng/mL. No statistical difference was found in respect to sports activity level before onset of the symptoms (P=0.09). Statistical analysis found a significant difference in vitamin D levels between patients with OD and patients without an OD (P=0.026). Conclusions: We found an unexpected high prevalence of vitamin D deficiency in juveniles diagnosed with OD presenting with significant lower mean 25-OH-D level compared with a control group. These results suggest that vitamin D deficiency is potentially associated with the development of OD. Thus, vitamin D deficiency might be an important cofactor in the multifactorial development of juvenile OD. For this reason, supplementation of vitamin D might not only be a potential additional therapy but also be a possible preventative factor in patients with juvenile OD. However, future prospective studies are needed to confirm this preliminary data. Level of Evidence: Level III—this is a case-control study.