Can rhBMP-2 Containing Collagen Sponges Enhance Bone Repair in Ovariectomized Rats?: A Preliminary Study

With an aging population the frequency of postmenopausal fractures is increasing. Methods to enhance the repair of osteoporotic bone repair therefore become more important to reduce the society burden of care. We asked if absorbable collagen sponges containing recombinant human bone morphogenetic protein-2 (rhBMP-2) have the potential to enhance bone repair. We randomly assigned 40 rats into the ovariectomy and sham operation groups. A segmental defect was created in the right tibia 12 weeks after ovariectomy. rhBMP-2-containing absorbable collagen sponges were implanted into the defect in half of the animals in each group. We analyzed radiographs and histological sections and performed three-point bending tests to assess repair. Radiological scores in the rhBMP-2 applied rats were higher than those in controls at the end of 8 weeks after tibial osteotomy. The specimens failed under higher loads in the rhBMP-2-applied groups and histology revealed a higher fracture healing score, including callus formation, bone union, marrow changes, and cortex remodeling. We observed no adverse tissue responses such as fibrous connective tissue formation and inflammatory cellular infiltration. rhBMP-2 in absorbable collagen sponges enhanced bone repair in segmental tibial defects of ovariectomized rats. The sponges with rhBMP-2 appeared to enhance bone repair.     

Bone graft tuberculosis outbreak in USA: Is it a concern in India?

Globally, 25% of the population is infected with tuberculosis, which poses a leading cause of death worldwide. The transmission of tuberculosis (TB) during organ transplant is reported in the literature whereas only one report has been published on the transmission of TB, during bone allograft transplantation. In the US, in May 2021, an outbreak of TB occurred in patients undergoing spine surgery with bone allograft. This bone graft was retrieved from 80 years deceased donor with latent TB, which was not diagnosed earlier. The recipients were started with a long course of anti-tuberculous drugs. This review narrates the pathway of TB spread among transplant recipients and the strategies to be followed while performing organ or tissue transplantation.     

Screw Fixation in Cancellous Osteoporotic Bone – First in Vitro Results with a Novel Augmentation Material

Background: Screw fixation during internal fixation of osteoporotic fractures can be difficult due to severe reduction of bone mass and structure in these patients. Material and Methods: The use of PMMA-bone cement to anchor implants in patients in a “combined osteosynthesis” has empirically been developed. The irreversibility of this methodology is currently limiting it to exceptional use in salvage cases of pathological fractures. A new degradable screw augmentation material was therefore developed on the basis of alkylene bis(oligolactoyl)methacrylates. The mechanical properties of this degradable polymer were tested by pull-out and torque tests in augmenting cancellous stainless steel screws in non-osteoporotic bovine cancellous bone blocks and in polypropylene blocks. In these tests, augmentation was improved significantly by the material. Results: The maximum pull-out force obtained showed an 256% increase compared to the bovine standard system. Screw torques measured were up to 400% higher than this standard for the new material. The in vitro degradation kinetics of the new polymer were tested in a standardized system showing an almost linear weight loss of the material of 2–3% per week between weeks 2 and 16. Conclusion: For further material development improved in vivo and in vitro models must be developed. They should include either considerable overdrilling in normal cancellous bone or human osteoporotic bone.     

Editorial Commentary: Polyurethane Meniscal Scaffold: A Perfect Fit or Flop?

The goal of using a synthetic scaffold to establish a biomechanically functioning meniscus or provide an equivalent meniscus substitute is not achieved by the polycaprolactone-polyurethane Actifit scaffold. Recent research, that did not include a control group, shows that the revision rate is significant, and any improvements in patient outcomes could reflect the associated reconstructive surgery. Based on these data and similar published reports, it is premature to conclude that this implant is clinically indicated. The technique is currently more flop than fit.     

Bone morphogenetic protein in complex cervical spine surgery: A safe biologic adjunct?

The advent of recombinant DNA technology has substantially increased the intra-operative utilization of biologic augmentation in spine surgery over the past several years after the Food and Drug Administration approval of the bone morphogenetic protein (BMP) class of molecules for indications in the lumbar spine. Much less is known about the potential benefits and risks of the “off-label” use of BMP in the cervical spine. The history and relevant literature pertaining to the use of the “off-label” implantation of the BMP class of molecules in the anterior or posterior cervical spine are reviewed and discussed. Early prospective studies of BMP-2 implantation in anterior cervical spine constructs showed encouraging results. Later retrospective studies reported potentially “life threatening complications” resulting in a 2007 public health advisory by the FDA. Limited data regarding BMP-7 in anterior cervical surgery was available with one group reporting a 2.4% early (< 30 d) complication rate (brachialgia and dysphagia). BMP use in the decompressed posterior cervical spine may result in neurologic or wound compromise according to several retrospective reports, however, controlled use has been reported to increase fusion rates in select complex and pediatric patients. There were no cases of de novo neoplasia related to BMP implantation in the cervical spine. BMP-2 use in anterior cervical spine surgery has been associated with a high early complication rate. Definitive recommendations for BMP-7 use in anterior cervical spine surgery cannot be made with current clinical data. According to limited reports, select complex patients who are considered “high risk” for pseudoarthrosis undergoing posterior cervical or occipitocervical arthrodesis or children with congenital or traumatic conditions may be candidates for “off-label” use of BMP in the context of appropriate informed decision making. At the present time, there are no high-level clinical studies on the outcomes and complication rates of BMP implantation in the cervical spine.     

Filler Cheeks: A Bright Idea? The “Eyes” Have It

The evolving field of facial volume restoration is changing our concept of facial rejuvenation. The older concept that "tighter is better" has been largely supplanted by a philosophy recognizing the importance of volume distribution as a defining characteristic of a more youthful face. It is well recognized that restoration of volume in the upper face can lessen or reverse the bottom-heavy, deflated appearance of the aging face. Perhaps of equal or greater importance is the change in light-reflectance patterns that illuminate the upper cheeks and the eyes. The resultant brighter and "perkier" cheeks can change the objective appearance and the patient's self perception of youthfulness. In this commentary, the author describes techniques to enhance outcomes and patient satisfaction and presents the results of a patient self-report pilot study assessing patient post-injection mood state and functioning.     

Bone disease in cystic fibrosis: what's new?

Cystic fibrosis (CF) is the most common autosomal recessive disease among Caucasians. It is due to a mutation in the cftr gene, which encodes the CF transmembrane conductance regulator (CFTR), a chloride channel located in the plasma membrane of mucus-secreting epithelial cells. Numerous other functions of the CFTR protein were identified recently. The survival gains achieved in CF patients over the last 30 years have led to the emergence of delayed complications, one of which is bone disease. The fracture risk is increased from late adolescence onward. Vertebral fractures have an estimated prevalence of 14% among CF patients and can cause severe respiratory complications. Bone mineral density (BMD) is below the age-specific range. Among young adults with CF, 23.5% have BMD values below the cutoff for osteoporosis. Z-scores, which are decreased in children with CF compared to healthy controls, diminish further in adolescence as a result of inadequate peak bone mass accumulation. Studies have shown increased bone resorption, most notably during infectious episodes, and disturbances in bone formation. The numerous pathophysiological mechanisms that contribute to diminish bone strength in CF patients include exocrine pancreatic failure with malabsorption, protein-calorie malnutrition, inflammation related to recurrent infection, and deficiencies in vitamins D and K. In addition, many recent studies support a role for abnormal CFTR function in the osteoblast dysfunction seen in CF. Appropriate diagnostic and therapeutic management of osteoporosis in CF patients is crucial. Risk factors for osteoporosis should be corrected to the extent possible. Oral bisphosphonate therapy may deserve consideration, particularly in adults.     

TGFβ Inhibition Stimulates Collagen Maturation to Enhance Bone Repair and Fracture Resistance in a Murine Myeloma Model

Multiple myeloma is a plasma cell malignancy that causes debilitating bone disease and fractures, in which TGFβ plays a central role. Current treatments do not repair existing damage and fractures remain a common occurrence. We developed a novel low tumor phase murine model mimicking the plateau phase in patients as we hypothesized this would be an ideal time to treat with a bone anabolic. Using in vivo μCT we show substantial and rapid bone lesion repair (and prevention) driven by SD-208 (TGFβ receptor I kinase inhibitor) and chemotherapy (bortezomib and lenalidomide) in mice with human U266-GFP-luc myeloma. We discovered that lesion repair occurred via an intramembranous fracture repair-like mechanism and that SD-208 enhanced collagen matrix maturation to significantly improve fracture resistance. Lesion healing was associated with VEGFA expression in woven bone, reduced osteocyte-derived PTHrP, increased osteoblasts, decreased osteoclasts, and lower serum tartrate-resistant acid phosphatase 5b (TRACP-5b). SD-208 also completely prevented bone lesion development in mice with aggressive JJN3 tumors, and was more effective than an anti-TGFβ neutralizing antibody (1D11). We also discovered that SD-208 promoted osteoblastic differentiation (and overcame the TGFβ-induced block in osteoblastogenesis) in myeloma patient bone marrow stromal cells in vitro, comparable to normal donors. The improved bone quality and fracture-resistance with SD-208 provides incentive for clinical translation to improve myeloma patient quality of life by reducing fracture risk and fatality. © 2019 American Society for Bone and Mineral Research.     

Urinary α and β C-Telopeptides of Collagen I: Clinical Implications in Bone Remodeling in Patients with Anorexia Nervosa

Fragments derived from degradation of type I collagen C-telopeptide (CTX) can be nonisomerized (α) or β-isomerized (β) depending on the age of bone; i.e., mainly the α form is derived from new bone and the β form from old bone. We have studied 41 female patients with anorexia nervosa (AN), aged 18.5 ± 2.2 years (range 16–24 years), and with an evolution time between 1.5 and 11 years, and 31 healthy control females (C), with a mean age of 19 ± 2.3 years (range 16–24 years). The AN patients showed a significant decrease in bone mass, with a mean Z-score of bone mineral density (BMD) of −3.2 ± 0.8 (range −0.9 to −5.4). The aim of our study was to determine the levels of urinary α- and β-CTX markers of bone resorption, the α/β ratio (α/β), and the level of bone alkaline phosphatase (bAP), a biochemical marker of bone formation, in order to relate them to the degree of osteopenia and the status of bone remodeling. Statistical analysis was by the Mann–Whitney test. The degree of osteopenia correlated with bAP levels (p= 0.0027) but not with the other parameters. Patients with AN were divided into three groups according to their levels of bAP: high (H), normal (N) or low (L). We found that BMD was significantly lower, and α- and β-CTX were significantly higher, in groups H and N than in group L. Bone AP correlated significantly with α-CTX (p= 0.0042) and α/β (0.0095) in the controls, but not with β-CTX, while in AN patients bAP correlated with β-CTX (p= 0.0000) and with α-CTX (p= 0.022) but not with the α/β ratio. The ratio CTX/bAP (resorption/formation) was similar in AN patients and controls. It is concluded that: (1) patients with AN have a high degree of osteopenia which correlated with bAP levels; (2) urinary CTX fragments found in AN patients seem to come mainly from old bone (β-CTX), while CTX found in healthy adolescent control females come from new bone (α-CTX). For this reason, α-CTX is more suitable than β-CTX for measuring bone resorption in controls and β-CTX is more suitable in patients with AN; (3) the resorption/formation ratio (CTX/bAP) was similar in AN patients and controls. From points (2) and (3) it is possible to suggest that, although bAP reflects bone formation in control females, this marker does not reflect effective bone mineralization in AN patients, a similar feature to that of patients with osteomalacia. Received: 20 January 1999 / Accepted: 28 May 1999     

Atrial Myxoma and Bone Changes: A Paraneoplastic Syndrome?

Atrial myxomas are the most common benign tumors of the heart and are difficult to diagnose due to a wide variety of presenting symptoms. We present a patient with a five-year history of visual loss, vertigo, ataxia, tinnitus, and bone lesions that resolved after diagnosis and resection of an atrial myxoma. This case not only highlights an unusual presentation of atrial myxomas but also raises the question of whether atrial myxomas can produce paraneoplastic syndromes, including bone abnormalities.