Paul S. Issack

Role of Wnt Signaling in Bone Remodeling and Repair

The Wnt genes encode a highly conserved class of signaling factors required for the development of several types of tissues including musculoskeletal and neural structures. There is increasing evidence that Wnt signaling is critical for bone mass accrual, bone remodeling, and fracture repair. Wnt proteins bind to cell-surface receptors and activate signaling pathways which control nuclear gene expression; this Wnt-regulated gene expression controls cell growth and differentiation. Many of the components of the Wnt pathway have recently been characterized, and specific loss-of-function or gain-of-function mutations in this pathway in mice and in humans have resulted in disorders of deficient or excess bone formation, respectively. Pharmacologically targeting components of the Wnt signaling pathway will allow for the manipulation of bone formation and remodeling and will have several orthopedic applications including enhancing bone formation in nonunion and osteoporosis and restricting pathologic bone formation in osteogenic tumors and heterotopic ossification.

Surgical correction of kyphotic deformity in spinal tuberculosis

PurposeApproximately 5% of patients with spinal tuberculosis will develop a severe kyphotic deformity resulting in increased potential for pain, spinal cord compression, cardiopulmonary dysfunction, costopelvic impingement and cosmetic concerns. This manuscript reviews the evaluation and surgical management of tuberculous kyphosis.MethodsThis is a review article.ResultsRisk factors for the development of severe kyphosis include those who develop spinal tuberculosis as children, multiple vertebral body involvement and thoracic spine involvement. These complications can be prevented by early diagnosis and treatment of spinal tubercular lesions at stages with little to no deformity. When tubercular lesions result in progression of kyphosis to more than 50 degrees, the deformity should be surgically corrected to avoid problems associated with sagittal imbalance. There are several operations described for the treatment of kyphosis secondary to tuberculous spondylitis. The type of the operation depends on the magnitude of correction required.ConclusionsAnterior, posterior and combined techniques as well as osteotomies and vertebral column resection have been described to correct spinal alignment and restore sagittal balance.

Sciatic Nerve Release Following Fracture or Reconstructive Surgery of the Acetabulum

BACKGROUND Sciatic neuropathy associated with acetabular fractures can result in disabling long-term symptoms. The purpose of this retrospective study was to evaluate the effect of sciatic nerve release on sciatic neuropathy associated with acetabular fractures and reconstructive acetabular surgery. METHODS Between 2000 and 2004, ten patients with sciatic neuropathy associated with an acetabular fracture were treated with release of the sciatic nerve from scar tissue and heterotopic bone. Additional surgical procedures included open reduction and internal fixation of the acetabulum (five patients), removal of hardware and total hip arthroplasty (three patients), and removal of hardware alone (one patient). The average age of the patients was forty-three years. All patients were followed with serial examinations and assessments for a minimum of one year (average, twenty-six months). RESULTS All patients had partial to complete relief of radicular pain, of diminished sensation, and of paresthesias after the nerve release. Four of seven patients with motor loss and two of five patients with a footdrop demonstrated improvement in function after the nerve release. No patient had evidence of worsening on neurologic examination after the release. CONCLUSIONS Sciatic nerve release during reconstructive acetabular surgery can decrease the sensory symptoms of preoperative sciatic neuropathy associated with a previous acetabular fracture. Motor symptoms, however, are less likely to resolve following nerve release.BACKGROUND Sciatic neuropathy associated with acetabular fractures can result in disabling long-term symptoms. The purpose of this retrospective study was to evaluate the effect of sciatic nerve release on sciatic neuropathy associated with acetabular fractures and reconstructive acetabular surgery. METHODS Between 2000 and 2004, ten patients with sciatic neuropathy associated with an acetabular fracture were treated with release of the sciatic nerve from scar tissue and heterotopic bone. Additional surgical procedures included open reduction and internal fixation of the acetabulum (five patients), removal of hardware and total hip arthroplasty (three patients), and removal of hardware alone (one patient). The average age of the patients was forty-three years. All patients were followed with serial examinations and assessments for a minimum of one year (average, twenty-six months). RESULTS All patients had partial to complete relief of radicular pain, of diminished sensation, and of paresthesias after the nerve release. Four of seven patients with motor loss and two of five patients with a footdrop demonstrated improvement in function after the nerve release. No patient had evidence of worsening on neurologic examination after the release. CONCLUSIONS Sciatic nerve release during reconstructive acetabular surgery can decrease the sensory symptoms of preoperative sciatic neuropathy associated with a previous acetabular fracture. Motor symptoms, however, are less likely to resolve following nerve release.

Recent Advances Toward the Clinical Application of PTH (1-34) in Fracture Healing

PTH 1-34, an active form of parathyroid hormone, has been shown to enhance osteoblastic bone formation when administered as a daily subcutaneous injection. The effect of the intermittent administration of PTH (1-34) is an uncoupling of bone turnover with an increase in bone mass and density and decrease in risk of vertebral and nonvertebral fractures. While PTH (1-34) has been used clinically to increase bone mass and reduce fracture risk in postmenopausal women with osteoporosis, there is increasing evidence that PTH (1-34) may promote fracture healing. Animal studies have demonstrated accelerated callus formation with enhanced remodeling and biomechanical properties of the healing fracture. Given these effects, PTH (1-34) will likely be used clinically to enhance fracture union in poor healing situations such as osteoporosis and recalcitrant nonunions.

Sciatic nerve injury associated with acetabular fractures.

Sciatic nerve injuries associated with acetabular fractures may be a result of the initial trauma or injury at the time of surgical reconstruction. Patients may present with a broad range of symptoms ranging from radiculopathy to foot drop. There are several posttraumatic, perioperative, and postoperative causes for sciatic nerve palsy including fracture–dislocation of the hip joint, excessive tension or inappropriate placement of retractors, instrument- or implant-related complications, heterotopic ossification, hematoma, and scarring. Natural history studies suggest that nerve recovery depends on several factors. Prevention requires attention to intraoperative limb positioning, retractor placement, and instrumentation. Somatosensory evoked potentials and spontaneous electromyography may help minimize iatrogenic nerve injury. Heterotopic ossification prophylaxis can help reduce delayed sciatic nerve entrapment. Reports on sciatic nerve decompression are not uniformly consistent but appear to have better outcomes for sensory than motor neuropathy.

Management of metastatic bone disease of the acetabulum.

Abstract Metastatic acetabular disease can be severely painful and may result in loss of mobility. Initial management may consist of diphosphonates, narcotic analgesics, radiation therapy, protected weight bearing, cementoplasty, and radiofrequency ablation. Patients with disease affecting large weight‐bearing regions of the acetabulum and with impending failure of the hip joint are unlikely to gain much relief from nonsurgical treatment and interventional procedures. The profound osteopenia of the acetabulum, limited healing potential of the fracture, and projected patient life span and function necessitate surgical techniques that provide immediate stable fixation to reduce pain and restore ambulatory function. Current reconstructive procedures, including cemented total hip arthroplasty, the saddle or periacetabular endoprosthesis, and porous tantalum implants, are based on the quality of remaining acetabular bone as well as the patients level of function and general health. Well‐executed acetabular reconstructions can provide durable hip joints with good pain relief and function.

Failure at the taper lock of a modular stemmed femoral implant in revision knee arthroplasty. A report of two cases and a retrieval analysis.

The Optetrak total knee arthroplasty system (Exactech, Gainesville, Florida) is the fifth in a series of total knee arthroplasty designs developed at the Hospital for Special Surgery1-3. The Optetrak implant retains the design concepts of the previous posterior stabilized Insall-Burstein-I (IB-I PS; Johnson and Johnson, Braintree, Massachusetts; Zimmer, Warsaw, Indiana) and Insall-Burstein-II (IB-II PS; Zimmer) posterior stabilized total knee implants2,4-7. A constrained condylar knee version of the Optetrak design has an elevated tibial post that, because of its higher and more squared design in comparison with standard posterior stabilized designs, provides greater varus-valgus and anteroposterior stability. The modular femoral and tibial components can accommodate stems through a taper junction. Traditionally, constrained condylar devices have been used with stem extensions to augment component fixation. The stem transfers the bending and torsion loads to the diaphysis and unloads the epiphyseal cancellous bone. From 1995 to 2006, 3886 of these constrained condylar stems were implanted at our institution. We report the cases of two patients who had failure in the male portion of the taper junction of the femoral component and stem extension. This study was performed under a protocol approved by the institutional review board of the Hospital for Special Surgery. Both patients were informed that data concerning the cases would be submitted for publication, and they consented. Case 1. A man underwent a right total knee arthroplasty for osteoarthritis in 1993 with use of the Insall-Burstein-II posterior stabilized knee prosthesis. The patient was sixty-three-years old, weighed 91 kg, and was 1.6 m tall at the time of the operation. He did well for nine years, until 2002, at which time aseptic loosening necessitated revision total knee arthroplasty with use of an Optetrak stemmed constrained condylar knee prosthesis. A constrained insert …

Alendronate inhibits PTH (1-34)-induced bone morphogenetic protein expression in MC3T3-E1 preosteoblastic cells.

The bisphosphonate class of antiresorptive drugs and active forms of parathyroid hormone (PTH (1–34)) have been used clinically to enhance bone mass and density in patients with osteoporosis. Abundant evidence suggests that the mechanism by which PTH (1–34) increases bone density is stimulation of osteoblast differentiation. Although bisphosphonates have been classically thought to increase bone density by inhibiting osteoclasts, there is increasing evidence to suggest that bisphosphonates have direct stimulatory effects on osteoblast differentiation. Interestingly, in patients with osteoporosis, combination therapy with bisphosphonates and PTH (1–34) is not synergistic in increasing bone density; bisphosphonates appear to blunt the effect of PTH (1–34). To begin to understand the mechanism governing the effects of these agents on osteoblasts and a possible explanation for their apparent antagonism, we examined the expression of several bone morphogenetic proteins (BMPs) in MC3T3-E1 preosteoblastic cells either untreated, or treated with alendronate, parathyroid hormone, or a combination of the two agents. We find by reverse transcriptase-polymerase chain reaction (RT-PCR) that while alendronate fails to induce the expression of any of the BMPs tested, several BMPs are induced by PTH (1–34). The induction of the PTH (1–34)-inducible BMPs is blocked with simultaneous alendronate treatment. These data suggest that alendronate interferes with PTH (1–34)-induced BMP gene transcription and provides a possible basis for the antagonism observed between the two agents in increasing bone density.

Axial Lumbosacral Interbody Fusion Appears Safe as a Method to Obtain Lumbosacral Arthrodesis Distal to Long Fusion Constructs

BackgroundCurrent methods to achieve lumbosacral interbody fusion have been complicated by approach-related morbidity, nerve root or cauda equina injury, or difficulty in implanting a large lordotic graft posteriorly. There is little information in the literature evaluating the presacral axial approach to the lumbosacral disc space.Questions/PurposesWhat are the short-term clinical and radiographic outcomes in patients undergoing axial lumbosacral interbody fixation and fusion at the end of long fusion constructs using the AxiaLIF implant (Trans1 Inc., Wilmington, NC, USA)? Furthermore, what complications are associated with this procedure?Patients and MethodsWe performed a retrospective evaluation of nine patients who underwent presacral axial lumbosacral interbody fixation and fusion at the end of long fusion constructs using the AxiaLIF implant. Preoperative diagnoses included adjacent segment degeneration below a long fusion construct for adult scoliosis and progressive sagittal plane deformity.ResultsThere were two pseudoarthroses, one at L4–5 and one at L5–S1. No major complications occurred. There were no significant differences in coronal or sagittal plane alignment at the time periods measured. There was no significant difference in implant position between immediate postoperative and final follow-up periods. There were significant postoperative improvements in Scoliosis Research Society-22 scores, specifically in the pain, self-image, and satisfaction with management domains.ConclusionsThe axial lumbosacral interbody fusion is a minimally invasive and safe method to obtain lumbosacral fixation and arthrodesis distal to a long fusion construct. Longer follow-up of larger numbers of patients are needed prior to recommending this procedure as a routine method to fuse L4–5 or L5–S1.

The axial transsacral approach to interbody fusion at L5-S1

Lumbosacral interbody fusion may be indicated to treat degenerative disc disease at L5-S1, instability or spondylolisthesis at that level, and severe neural foraminal stenosis resulting from loss of disc space height. In addition, L5-S1 interbody fusion may provide anterior support to a long posterior fusion construct and help offset the stresses experienced by the distal-most screws. There are 3 well-established techniques for L5-S1 interbody fusion: anterior lumbar interbody fusion, posterior lumbar interbody fusion, and transforaminal lumbar interbody fusion. Each of these has advantages and pitfalls. A more recently described axial transsacral technique, utilizing the presacral corridor, may represent a minimally invasive approach to obtaining lumbosacral interbody arthrodesis. Biomechanical studies demonstrate that the stiffness of the axial rod is comparable to existing fixation devices, suggesting that, biomechanically, it may be a good implant for obtaining lumbosacral interbody fusion. Clinical studies have demonstrated good early results with the use of the axial transsacral approach in obtaining lumbosacral interbody fusion for degenerative disc disease, spondylolisthesis, and below long posterior fusion constructs. The technique is exacting and complications can be major, including rectal perforation and fistula, loss of correction, and pseudarthrosis.