Gains made towards treatment of rare bone disease . . . Diagnosed in toddlers, X-linked hypophosphatemia (XLH) is the most common form of heritable rickets, in which soft bones bend and deform, and tooth abscesses develop because infections penetrate soft teeth that are not properly calcified. Researchers at McGill University (Hamilton, Ontario) and the Federal University of Sao Paulo (Brazil) have identified that osteopontin, a major bone and tooth substrate protein, plays a role in XLH. Their discovery may pave the way to effectively treating this rare disease. The findings were made by the laboratories of Marc McKee, a professor in the Faculty of Dentistry and the Department of Anatomy and Cell Biology at McGill University, and of Nilana M.T. Barros, a professor at the Federal University of Sao Paulo. The team built upon previous research that had shown that mutations in the single gene PHEX are responsible for causing XLH. The results of this latest research by Drs. McKee and Barros will be published in the March issue of the Journal of Bone and Mineral Research. “XLH is caused in part by renal phosphate wasting, which is the urinary loss from the body of phosphate, an important building block of bones and teeth, along with calcium,“ says Prof. McKee. “In pursuing other factors that might contribute to XLH, we used a variety of research methods to show that PHEX enzymatic activity leads to an essentially complete degradation of osteopontin in bones.“ This loss of osteopontin, a known potent inhibitor of mineralization (or calcification) in the skeleton and dentition, normally allows bones and teeth to mineralize and thus harden to meet the biomechanical demands placed on them. In XLH patients lacking functional PHEX enzyme, osteopontin and some of its smaller potent inhibitory peptides are retained and accumulate within the bone. This prevents their hardening and leads to soft deformed bones such as bowed legs (or knock-knees) seen in toddlers. While not life-threatening, this decreased mineralization of the skeleton (osteomalacia), along with the soft teeth, soon leads to a waddling gait, short stature, bone and muscle pain, weakness and spontaneous tooth abscesses. The fact that these symptoms are only partially improved by the standard treatment with phosphate - which improves circulating phosphate levels - prompted the researchers to look for local factors within the bone that might be blocking mineralization in these patients. “With this new identification of osteopontin as a substrate protein for PHEX,“ says Professor Barros, “we can begin to develop an enzyme-replacement therapy to treat XLH patients who have nonfunctional PHEX, much as has been done using a different enzyme to treat another rare bone disease called hypophosphatasia.“

Diabetes not found to impact infection risk, surgical outcomes . . . Patients with diabetes were no more likely to suffer infection, deep vein thrombosis (a deep vein blood clot) or other complications following total knee replacement (TKR) than patients without diabetes, according to new research published online, in advance of its publication in the March 2013 Journal of Bone and Joint Surgery (JBJS). The study authors sought to determine whether or not blood sugar level (glycemic control) influenced outcome in TKR. Fifty-two percent of people with diabetes have arthritis. Previous studies have found that poor glycemic control may cause postoperative complications. Researchers reviewed records of more than 40,000 Kaiser Permanente patients who underwent TKR between January 2001 and December 2009, of whom 7,567 (18.7%) had diabetes, 464 underwent revision surgery (1.1%), and 287 (.7%) developed a deep infection. Of the total number of patients, 12.5% had controlled diabetes and 6.2% had uncontrolled diabetes. In this study, researchers found no significant increase in risk for TKR revision, deep infection or deep vein thrombosis in patients with diabetes - controlled or uncontrolled - compared to patients without diabetes. Patients with diabetes were more likely than patients without diabetes to be obese (56.7% compared with 40.35), and have a severe comorbidity (related disease/condition) burden (17.5% compared with 2.4%). The rates of deep infection, deep vein thrombosis and pulmonary embolism (when a blood clot reaches the lungs) were low, and comparable in the controlled and uncontrolled diabetic groups to the non-diabetic group. Uncontrolled diabetics did not appear to be associated with an increased risk of myocardial infarction (heart attack) or rehospitalization. Controlled diabetics had a slightly greater percentage of revisions (1.7%) compared to uncontrolled diabetics (1.2 %). “This current study suggests that patients with diabetes who have higher glucose levels may not be at greater risk of poor surgical outcomes,“ said Annette L. Adams, PhD, MPH, of the Kaiser Permanente Southern California Department of Research & Evaluation. “There appear to be other factors at play, and patients and their providers need to consider multiple factors, including but not limited to diabetes status, as they make decisions about whether to have this surgery.“

OsteoMed launchs OsteoVation QWIK bone void filler . . . OsteoMed (Addison, Texas), a privately held device company specializing in small bone implants and biologics, reported the launch of OsteoVation QWIK. OsteoVation QWIK consists of a proprietary composite of calcium phosphate and calcium sulfate granules, and is indicated to fill bony voids and gaps of the skeletal system. The unique formulation creates a macroporous construct that allows faster bone remodeling, while maintaining targeted compressive strength. OsteoVation QWIK is packaged in both impact and Inject formulas that provide surgical options for both traditional open or minimally-invasive surgical procedures. Both formulations are osteoconductive and provide a scaffold to enhance the bone during the healing process. Dave Kelly, vice president of Small Bone Orthopedics said, “All of us at OsteoMed are excited about the market introduction of OsteoVation QWIK. This new bone void filler expands our current biologic portfolio and provides surgeons with another best-in-class product from OsteoMed. OsteoVation QWIK is the perfect complementary product to our existing Small Bone Orthopedics product offering. OsteoVation QWIK provides surgeons the ability to incorporate this innovative bone void filler while using other OsteoMed products such as ExtremiFix, our Large Cannulated Screw System, Hand Plating System (HPS) and the Foot Plating System (FPS) where indicated. OsteoVation QWIK is just one of several exciting new products scheduled to launch in 2013.“ OsteoMed was founded in 1990 with the principle mission of improving patient outcomes through the development of advanced medical devices. Working in close collaboration with leading surgeons to create patient-focused solutions, OsteoMed services the small bone orthopedics, Craniomaxillofacial, Neuro, and Spine surgical specialties. Each business unit has dedicated resources to assure focus on addressing unmet clinical needs that are unique to each surgical specialty.

Radiographs taken immediately after shoulder surgery are of poor quality, study finds . . . Researchers in this study conducted at Penn Presbyterian Medical Center (Philadelphia) concluded the majority of radiographs taken immediately after shoulder arthroplasty are of poor quality and recommended the practice be discontinued. “Routine [postanesthesia care unit] PACU radiographs, in the absence of a specific indication, may result in poor-quality images,“ Surena Namdari MD, MSc, and colleagues wrote in the study abstract. “Elimination of these radiographs and radiographic interpretation after shoulder arthroplasty may reduce charges without changing clinical care.“ In comparing radiographs from 283 patients who had images taken immediately after surgery to 241 patients who had their radiographs taken at a later date, Namdari and colleagues found all images taken right after surgery comprised of single-view radiographs with 88% internal rotation, according to the abstract. Additionally, the imaging charges for the group of patients with radiographs taken immediately after surgery was $64,524. Images taken immediately after surgery were underpenetrated 71% of the time and none of them influenced postoperative care or were considered an adequate baseline. Radiographs from patients taken at a later date tended to be multi-view imaging with 83% considered adequate as a baseline, according to the abstract.

— Compiled by Holland Johnson, MDD Executive Editor