Tag Archive | zoledronic acid

Getting to the Core of Bone Marrow Lesions

Bone Marrow Lesion for OBuzzThis post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

The terms “bone marrow edema,” “bone marrow lesion” (BML), and “bone bruise” are often used interchangeably to refer to areas in cancellous bone that have hyperintense marrow signal in fluid-sensitive, fat-suppressed MRI sequences. Although most commonly observed in knee MRIs, BMLs can be seen in a variety of joints. In the hip, they are seen in transient osteoporosis and rapid-onset osteoarthritis. The term “bone bruise” is often specifically applied in the setting of an injury, such as lateral tibial plateau hyperintense changes that are seen after an anterior cruciate ligament rupture.

In the setting of knee osteoarthritis, BMLs are a response to degeneration of menisci, articular cartilage, synovium, or bone itself. One of the mechanisms associated with BMLs seems to be secondary to circulatory response and bone turnover. In one study covered in a 2017 review article1, patients with OA and associated BMLs were randomized to receive the bone antiresorptive agent zoledronic acid (ZA) or placebo. At 6 months, VAS pain scores in the ZA group were reduced by ZA, the reduction in BML area was greater in the ZA group than in the placebo group, and a greater proportion in the ZA group achieved a clinically significant reduction in BML size (39% vs. 18%, p <0.044). A larger study is planned to further define the relationship between reduction in BML size and pain scores.

Regarding “crosstalk” between subchondral bone and articular cartilage in joint disease, recent data suggest that numerous canals and porosities connect the bone to cartilage at the interface. Treatment of the bone compartment with antiresorptives and anti-TGF-β at specific early time points has been shown to have chondroprotective effects in animal models. Additionally, one study identified s14-3-3ε, a short extracellular protein, as a mediator critical in the communication between subchondral bone and cartilage in OA. This may prove to be a potential target for therapeutic or prognostic use.

Numerous articles have outlined the abundance of trabecular microfractures seen in areas where BMLs are present. A commonly held hypothesis is that resorption cavities caused by bone remodeling can act as stress concentrations, promoting further microdamage and leading to a cycle of damage-remodeling-damage. Some individuals may be more prone to rapid bone turnover and thus more prone to developing bone edema.

When your clinical attention is directed to BMLs, their shape and extent may influence nonsurgical treatment decisions. Conservative management may be directed by a better understanding of how BMLs contribute to pain and OA progression.

Reference

  1. Alliston T, Hernandez CJ, Findlay DM, Felson DT, Kennedy OD. Bone marrow lesions in osteoarthritis: What lies beneath. J Orthop Res. 2017 Dec 21. doi: 10.1002/jor.23844. [Epub ahead of print] PMID: 29266428

What’s New in Primary Bone Tumors

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from studies cited in the December 17, 2014 Specialty Update on primary bone tumors:

Chondrosarcoma

–MicroRNA-145, an inhibitor of cell growth, was expressed at abnormally low levels in chondrosarcoma, lending credence to the hypothesis that underexpression of microRNA-145 plays a role in cancer development.

–Osteoclasts enhance the ability of chondrosarcoma to invade bone, but that invasion that can be partially halted by zoledronic acid.

–There is increased activity of the glycolysis-associated enzyme lactate dehydrogenase-A (LDHA) in chondrosarcoma.

–Density and location of new blood-vessel formation may be an important prognostic factor in chondrosarcoma.

–Conditional survival in patients with chondrosarcoma improves with each year of survival, but even patients who survive ten years after diagnosis cannot be considered cured.

Chordoma

–Variants of T transcription factor play a role in the pathophysiology of familial and sporadic chordoma.

–In patients with primary sarcomas of the spine, proton radiation plus surgery yielded local control rates of 85% at eight years.

Osteosarcoma

–Expression of the glucose transporter Glut-1 correlated with worse outcomes in patients with osteosarcoma.

–Secondary malignant neoplasms were found in 2.1% of long-term survivors of osteosarcoma.

–Use of fluorescence-guided surgery in a mouse model of osteosarcoma allowed reduction in the amount of residual tumor and improved disease-free survival.

–Among patients with high-grade osteosarcoma with soft-tissue extension, four parameters—tumor location, intracapsular extension, Huvos grade, and alkaline phosphatase level—may help predict which individuals will eventually develop metastases.

–In 45 patients with local recurrence but no metastases, the 10-year survival rate was 13%; most local recurrences were in soft tissue, not bone.

–Mid-therapy PET imaging may be useful to physicians in assessing response to chemotherapy.

Ewing Sarcoma

–Twenty-one percent of Ewing sarcoma samples had deletions of the STAG2 gene, and patients with STAG2 deletions had more aggressive tumors.

Soft-Tissue Sarcoma

–Among patients who also had surgery, intensity-modulated radiation therapy (IMRT) was associated with a lower local recurrence rate compared to conventional external-beam radiation.

–Six-month progression-free survival was 58% among 91 patients in a phase-II clinical trial of a hypoxia-activated cytotoxic agent (TH-302) used with doxorubicin.

–In a follow-up protocol comparison, radiography was noninferior to CT in terms of overall survival rate and disease-free survival.

–Ninety-five percent of 867 soft-tissue sarcoma patients who developed a recurrence did so within 8.6 years, raising questions about the usefulness of following patients beyond 10 years.

Reconstruction

–Due to high complication rates, intercalary allograft reconstruction after tumor resection should be reserved for defects of 15 cm or less, and plate-and-screw fixation should be used rather than intramedullary-nail fixation.

–Thirty-six patients who received frozen orthotopic autograft during reconstruction demonstrated a 10-year autograft survival rate of 80%.

–Patients who underwent pelvic reconstruction had a higher infection rate (26%), compared with those who did not undergo pelvic reconstruction (15%).