New Method for Healing a Pathologic Fracture Using the BioChem Bracing System

Ernest C. Chisena M.D. M.S.

St. Catherine of Siena Medical Center & VA Medical Center, Northport NY

Robert S. Chisena
Dept. of Mechanical and Nuclear Engineering Penn State University, University Park, PA

Corresponding Author
Ernest C. Chisena M.D. M.S. 101 Centerport Road Centerport, New York 11721 Tel 631-261-0010 Fax 631-261-7984 echisenamd@gmail.com (can publish)

Disclosure
Ernest C. Chisena authored and co-authored patents describing the bracing concept used in this case study.

Contents
Abstract ........................................................................................................................................... 4 Case Report ..................................................................................................................................... 5 Discussion ....................................................................................................................................... 9 References ..................................................................................................................................... 12

Abstract
This article describes a patient with adenocarcinoma of the lung who incurred a pathologic fracture of the distal femur through a metastasis. The approximate incidence of bone metastasis in advanced lung cancer patients ranges from 30-40%. The proximal long bones are the most commonly involved. The median survival for patients with bone metastases is a dismal <6 months. Our patient had a positive response to a bracing device that increased the pressure in the soft tissues of the metastatic tumor. The reversal of the bony lysis and the massive callus that bridged the fracture with this treatment is reportable. Presently, treatments of bony metastases from lung cancer include chemotherapy (including bisphosphonates), radiation, and surgery. These treatments are primarily to relieve pain. Bone healing was not the endpoint of studies of radiation treatments for lung metastases. Neoplastic involvement in bone arise from the dysregulation of the normal remodeling process, usually tightly controlled in balance between the bone resorption functions of osteoclasts and the remodeling and formation mediated by osteoblasts.4 Bisphosphonates are specific inhibitors of osteoclast activity and inhibit bone resorption.5 They have been shown to inhibit tumor cell invasion and adhesion to bone matrix.6 The primary endpoints in studies of treatment of lung metastases with bisphosphonates are the skeletal-related events (pathological fracture, spinal cord compression or hypercalcemia) not bone healing.7 Conventional treatments of bony metastases from lung cancer are palliative, rarely achieving bone healing. This article describes an alternative treatment, and the patients positive response to an increase in the soft tissue pressure within the metastatic femoral lesion. (Associate Fig 6A with the abstract)

Case Report
An 82 year old female presented with left thigh pain after falling and sustaining a pathologic fracture of the left distal femur (Figure 1 & Figure 2).

Figure 1. Lateral X-Ray of the Distal Femur with the Pathologic Fracture

Figure 2. Anterior-Posterior X-Ray of the Distal Femur. This radiograph shows the pathologic fracture with an overlying deforming element (shown with white outline).

Past medical history included adenocarcinoma of the lung, carcinoma of the sigmoid colon, breast carcinoma, coronary artery disease with myocardial infarction, and severe chronic obstructive pulmonary disease. Physical examination revealed a cachectic appearing white female in no acute distress. On the left side of the chest, she had decreased breast sounds and hemi-thoracic expansion. In addition, there was a healed left mastectomy scar. The left lower extremity was shortened, and the left thigh was deformed. X-rays of her chest revealed complete opacification of the left hemi-thorax (Figure 3).

Figure 3. Anterior-Posterior X-Ray of the Chest

X-ray examination of the left distal femur revealed a destructive metastatic lesion with a pathologic fracture through it (Figure 4).

Figure 4. Close-up Anterior-Posterior X-Ray of the Distal Femur. This radiograph shows the lytic destruction of the bone.

Her pulmonary physician recommended against any surgical treatment requiring general anesthesia. Under local anesthesia, a large Steinmann pin was placed across her proximal tibia for traction. To improve alignment and stimulate healing , a thigh cuff was applied with deforming elements placed anteriorly and laterally (Figure 5 & Figure 6).10 These deforming elements had radiographic markers embedded within them.

Figure 5. Bracing Device with Deforming Element. The device was placed on the patients thigh with an anterior deforming element.

Figure 6. Lateral X-Ray of the Distal Femur. Shows brace compressing the anterior soft tissue.

After 6 weeks, the bony lysis caused by the metastatic lesion was reversed and massive callus bridged the fracture (Figure 7). After 8 weeks, the fracture was sufficiently healed to mobilize the patient out of bed into a chair. At this time, the radiation treatment began. After 12 weeks, the fracture was sufficiently healed to allow the patient to ambulate using a walker (Figure 8. Anterior-Posterior X-Ray of the Distal Femur showing the Reversal of the Bony Lysis& Figure 9. Patient Bearing Weight on the Healed Pathologic Femoral Fracture.

Figure 7. Lateral X-Ray of the Distal Femur showing Massive Callus Bridging the Fracture.

Figure 8. Anterior-Posterior X-Ray of the Distal Femur showing the Reversal of the Bony Lysis

Figure 9. Patient Bearing Weight on the Healed Pathologic Femoral Fracture

Discussion
Clearly the reversal of the bony lysis and the massive callus that bridged the fracture with bony healing at the site of a metastatic lesion is noteworthy. We propose that an increase in pressure in the soft tissues surrounding the fracture enhanced its healing.10 The concept of applying pressure around a fracture to permit healing has precedent. According to Sarmiento et.al, invok[ing] firm compression of the soft tissue surrounding the fractured bone applied by the rigid walls of the brace permits uninterrupted osteogenesis. 11 Although the authors utilized this concept, the exact pressure distributions that are created in the soft tissues by the walls of the brace are not specified. The cuff used in their study has a coaptable cylindrically symmetric interface, which is similar to a tourniquet. The pressure distribution in the soft tissues created by a tourniquet has been studied in detail by McLaren and Rorabeck.9 One would expect that the pressure distribution created by Sarmientos coaptable brace would be similar to that of a tourniquet which produces a circumferential increased pressure. The bracing system used on the patient in this case report consists of a cylindrical coaptable cuff containing a deforming element (Figure 10). The deforming element was positioned over the soft tissue component of the metastatic lesion at the fracture site (Figure 11). The presence of the deforming element creates an asymmetric deformation of the soft tissues. This bracing geometry was studied with finite element analysis that modeled the soft tissue as a hyper-elastic material. The pressure distribution that was predicted by this analysis is a cone of elevated pressure extending from the deforming element down to the bone and lower pressure on the side opposite of the deforming element (Figure 12).

Figure 10. Schematic Cross-Section Representation of the BioChem Bracing System.

Figure 11. Long leg fracture brace with a deforming element in place after the pathologic fracture healed sufficiently to remove traction

Figure 12. Finite Element Pressure Plot of BioChem Bracing System. The FEA is modeling the pressure profile of the cross-section of a thigh. Note the cone of elevated pressure extending from the deforming element (MX) down to the bone (center).

This pressure distribution would cause a decrease in blood flow beneath the deforming element.8 This asymmetric deformation is predicted to produce a unique axially asymmetric pressure distribution, different than the axially symmetrical pressure distribution created by Sarmientos cuff. Ashtons animal studies established the relationship between blood flow and soft tissue pressure. Her work supports our claim that the blood flow in the soft tissues between the deforming element and the bone is diminished. The asymmetric geometry of the brace, a key to its design, increases soft tissue pressure around the fracture and in the metastatic tissue. This causes a decrease in blood flow below the deforming element. These conclusions are also consistent with the human experimental results published by Ashton. We further hypothesize that decreased blood flow in the soft tissues diminishes the local oxygen tension. This reduction is referred to as stagnant hypoxia. This is consistent with the conservation of mass which states that local oxygen tension reflects the balance between oxygen delivery and oxygen consumption. As enunciated by Fick, the amount of oxygen consumed per

unit time in a blood perfused tissue is equal to blood flow times the difference in arterial and venous concentration of oxygen. The stagnant hypoxia created by the diminished blood flow surrounding the fracture may have influenced the osteoblasts by stabilizing the hypoxic inducing factor (HIF)-1 pathway.13 This may explain the new bone bridging the fracture. A mechanism to explain the reversal of the bone lysis caused by the tumor is not so forthcoming. It is known that hypoxia exists within a metastatic lesion.12 Elevated levels of hypoxic inducing factor have been measured within tumor tissue causing an elevation of vascular endothelial growth factor (VEGF), which stimulates angiogenesis.12 The increased pressure and tissue deformation caused by the deforming elements may have disrupted the network of new friable blood vessels (angiogenesis). It would seem prudent that the effects of tissue deformation on metastatic tissue and the perturbation of the oxygen tension within that tissue receive further study. Since the time of writing this report, a second patient with adenocarcinoma of the lung with a pathologic fracture through the proximal radius was treated with a bracing device that increased the pressure in the soft tissues of the metastatic tumor resulting in a similar bone healing response.

References
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12. Shah, S. Hypoxia in tumor angiogenesis and metastasis: evaluation of VEGF and MMP over-expression and down-regulation of HIF-1a with RNAi in hypoxic tumor cells. Pharmaceutical Science Master's Theses. 2010;18. 13. Wan C, Gilbert SR, Wang Y, Xuemei C, Shen X, Ramaswany G, Jacobsen KA, Alaql ZS, Eberhardt AW, Gerstenfeld LC, Einhorn TA, Deng L, Clemens TL. Activation of the hypoxia-inducible factor-1 pathway accelerates bone regeneration. PNAS. 2007; 105(2): 686-691.