John S. Hwang

Long-term bisphosphonate usage and subtrochanteric insufficiency fractures

For over a decade, bisphosphonate administration has evolved and become the cornerstone of the prevention and treatment of fragility fractures. Millions of post-menopausal women have relied on, and continue to depend on, the long-acting, bone density-maintaining pharmaceutical drug to prevent low-energy fractures. In return, we have seen the number of fragility fractures decrease, along with associated costs and emotional benefits. However, with any drug, there are often concerns with side effects and complications, and this unique drug class is seeing one such complication in atypical subtrochanteric femoral fracture, counterproductive to that which it was designed to prevent. This has created concern over long-term bisphosphonate administration and its potential link to these atypical fractures. There is controversial evidence surrounding such a definitive link, and no protocol for managing these fractures. This review offers the latest information regarding this rare but increasingly controversial adverse effect and its potential connection to one of the most successful forms of treatment that is available for the management of fragility fractures.

Potentiation by the Tetraphenylboron Anion of the Effects of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine and Its Pyridinium Metabolite

Abstract: The 1‐methyl‐4‐phenylpyridinium species (MPP+) is the four‐electron oxidation product of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and is widely assumed to be the actual neurotoxic species responsible for the MPTP‐induced destruction of dopaminergic neurons. MPTP is oxidized by the enzyme monoamine oxidase‐B to a dihydropyridinium intermediate which is oxidized further to MPP+, an effective inhibitor of the oxidation of the Complex I substrates glutamate/malate in isolated mitochondrial preparations. In the present study, the tetraphenylboron anion (TPB) greatly potentiated the inhibitory effects of MPP+ and other selected pyridinium species on glutamate/malate respiration in isolated mouse liver mitochondria. At 10 μM TPB, the potentiation ranged from approximately 50‐fold to greater than 1,000‐fold for the several pyridinium species tested. In other experiments, TPB greatly enhanced the accumulation of [3H]MPP+ by isolated mitochondrial preparations. This facilitation by TPB of MPP+ accumulation into mitochondria explains, at least in part, the potentiation by TPB of the above‐mentioned inhibition of mitochondrial respiration. Moreover, TPB addition increased the amount of lactate formed during the incubation of mouse neostriatal tissue slices with MPTP and other tetrahydropyridines. The administration of TPB also potentiated the dopaminergic neurotoxicity of MPTP in male Swiss‐Webster mice. All of these observations, taken together, are consistent with the premise that the inhibitory effect of MPP+ on mitochondrial respiration within dopaminergic neurons is the ultimate mechanism to explain MPTP‐induced neurotoxicity.

From amputation to limb salvage reconstruction: evolution and role of the endoprosthesis in musculoskeletal oncology.

In 1943, Austin Moore developed the first endoprosthesis fashioned from Vitallium, providing the first alternative to traditional amputation as primary treatment of bone tumors. The success of the Vitallium endoprosthesis has since then led to the development of new materials and designs further advancing limb salvage and reconstructive surgery. Combined with the advent of chemotherapy use and imaging advances, conservative treatment of musculoskeletal tumors has expanded greatly. As the implantable options increased with the development of the Lewis expandable adjustable prosthesis and the noninvasive Phenix Growing prosthesis, receiving the diagnosis of a bone tumor no longer equates to automatic limb loss. Our review details the history and development of endoprostheses throughout orthopedic oncology in the treatment of musculoskeletal tumors.

Malignant Granular Cell Tumor of the Thigh

Malignant granular cell tumor is a rare neural tumor characterized by abundant granular-appearing tumor cells. These tumors account for <2% of all granular cell tumors. Unlike its benign counterpart, a malignant granular cell tumor presents primarily in the lower limb and is notably larger. Both the uncommon occurrence of malignant granular cell tumors and its similarities in feature with their benign counterparts make diagnosis of this particular malignancy difficult. By 1998, Fanburg-Smith et al developed a diagnostic criteria in which granular cell tumors were divided into 3 categories-benign, atypical, and malignant-based on 6 histological characteristics of the tumor: necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity, high nuclear-to-cytoplasmic ratio, and pleomorphism. This article presents a case of a large malignant granular cell tumor in the right thigh of a 69-year-old woman. Gross examination of the mass showed the well-demarcated, tan, white tumor measuring 18.2 cm long and 7.6 cm wide at its largest width. Histological examination of the mass, performed by an oncological pathologist, demonstrated foci of tumor necrosis, scattered apoptotic cells, prominent nucleoli, increased nuclear-to-cytoplasmic ratio, increased mitotic activity, and areas of spindling with significant atypia. To our knowledge, this is the largest reported case of malignant granular cell tumor in the lower limb diagnosed using the histological criteria established by Fanburg-Smith et al. This case stresses the importance of thorough evaluation in instances of atypical granular cell tumor presentations.

Infected Total Femoral Replacements: Evaluation of Limb Loss Risk Factors

A complication of total femoral replacement (TFR) is periprosthetic infection. Studies have shown that infected endoprostheses have a significant amputation rate, as high as 36.7%. This study examined possible risk factors that may attribute to unsalvageable TFRs following periprosthetic infections, including age, sex, primary vs secondary TFRs, number of irrigation and debridements, recent history of periprosthetic infection, early vs late infection, use of antibiotic cement, and the number of postoperative antibiotics. In a retrospective chart review, 10 patients who had periprosthetic infections of their TFRs were identified from our orthopedic surgical database between 2000 and 2010. Seven of 10 TFRs were unsalvageable due to infection. The 2 greatest risk factors that influenced unsalvageable TFR were age older than 50 years and recipients of secondary TFRs. All 6 patients older than 50 years had unsalvageable TFRs, whereas 1 of 4 patients younger than 50 years had an unsalvageable TFR (P<.05). Similarly, all 6 patients who received secondary TFRs had unsalvageable TFRs, whereas 1 of 4 patients who received a TFR as the primary method of treatment had an unsalvageable TFR (P<.05). No other risk factors showed statistical significance or could be identified as possible risk factors. Surgeons should educate patients who fall into high-risk categories about the benefits of early intervention, such as amputation, that could prevent additional surgeries and decrease the lengths of hospitalizations.

Septic Arthritis of the Hip Caused by Group B Streptococcus in a Postpartum Patient

Group B streptococcus is the leading cause of neonatal meningitis and sepsis, affecting approximately 9600 newborns in the United States annually1. Classically associated with newborn infection, it is also associated with 50,000 cases of pregnancy-connected morbidity, including urinary tract infection, chorioamnionitis, postpartum endometritis, and bacteremia1,2. Deutscher et al. stated that postpartum women have a “marked predisposition” for group B streptococcal infection3. While rare, cases of septic arthritis of the hip involving group B streptococcus have been reported, including one by Howell and Sheddon4. We present a postpartum woman with group B streptococcal septic arthritis of the right hip. This case highlights the importance of early diagnosis and awareness of septic arthritis in postpartum patients. The patient was informed that data concerning the case would be submitted for publication, and she provided consent. A thirty-eight-year-old woman, seventeen weeks postpartum, presented to the Emergency Department with right-sided hip pain, a progressive limp, and refusal to bear weight on the right lower extremity. Before visiting our Emergency Department, she had been diagnosed with radicular pain and had been prescribed analgesics, which proved ineffective. The pain initially had presented two weeks postpartum and had increased over the next four months. She denied fever, chills, and trauma. She had had an uneventful pregnancy and a vaginal delivery at full term. She was neither tested nor treated for group B streptococcus prior to delivery. She denied current tobacco, alcohol, and drug use but did have a history of cigarette smoking. Medical history and family history were unremarkable. On physical examination, the patient walked a maximum of two paces with an antalgic gait. She had decreased range of motion of the right hip, which worsened with internal rotation and extension. She was afebrile. White blood-cell (WBC) count …

Multiple Giant Cell Tumors of Tendon Sheath Found within a Single Digit of a 9-Year-Old

Giant cell tumor of tendon sheath is one of the most common soft tissue tumors of the hand. These tumors typically occur in the third or fourth decade of life and present as solitary nodules on a single digit. Currently, the greatest reported number of lesions found within a single digit is five. Although uncommon, giant cell tumor of tendon sheath does occur in the pediatric population. Herein we present a report of a rare case of GCTTS in a child in which seven lesions were identified within a single digit—the greatest number of lesions within a single digit reported to date.

The Antibiotic Nail in the Treatment of Long Bone Infection: Technique and Results

Antibiotic cement nails provide a useful and relatively simple technique to treat intramedullary osteomyelitis of the long bones. These devices provide stability as well as local, targeted antibiotics, which are both critical aspects of osteomyelitis management. Additionally, the use of a threaded core is a critical component of successful cement nail assembly. With adherence to the simple principles outlined in this review, surgeons can expect reliably good results using these drug-delivery implants.

Identifying impending pathologic fractures and treatment considerations in patients with metastatic bone disease

Over a half million people succumb to cancer-related illness each year in the United States, well more than half of whom have evidence of metastatic bone disease on postmortem examination. The treatment of this disease is primarily palliative but can greatly increase a patient’s quality of life. Although there are risks involved with surgery, the effects of a pathologic fracture on quality of life may outweigh the risks. Unrelenting pain, instability, impending fracture, or neurologic compression are indications for surgery; however, in patients in whom surgery is deemed inappropriate, options include the use of pharmaceuticals, radiation therapy, and radiofrequency ablation. This review focuses on the early identification of high-risk tumors before fracture occurs and discusses treatment options.

Local adjuvants for benign aggressive bone tumors

Benign aggressive bone tumors include giant cell tumors, chondroblastomas, unicameral bone cysts, and aneurysmal bone cysts. They are neoplasms that rarely metastasize but may be locally aggressive and frequently recur. Treatment formerly included wide resection but now increasingly involves curettage to preserve the involved limb and prevent surgical complications. Local adjuvants are used to expand the zone of tumor death and lower recurrence rates. Here, local adjuvants are discussed, including their mechanism, use in studies, and related complications.