Normal bone activity includes osteoclasts that wear away bone and osteoblasts that build up new bone. A pathologic fracture in a person with cancer is a fracture that occurs in a bone because it is weakened by primary or metastatic disease, sometimes as a consequence of minimal trauma. Other diseases and conditions that involve pathologic fractures include Paget’s disease, fibrous dysplasia, tuberculosis, osteoporosis, pyogenic osteomyelitis, osteoid osteoma, gout, Gorham’s disease, fibrous dysplasia, and benign bone cysts. The most common condition associated with noncancerous pathologic fractures is osteoporosis.
Bone metastases are a common cause of morbidity in cancer patients (Rubens, 1998). Pathologic factures impair ambulation and can cause spinal cord compression and severe neurologic impairment. Pathologic fractures rarely heal if left untreated.
When tumor cells become lodged adjacent to bone, the cells of the bone produce growth factors and angiogenic factors that support tumor growth. Some tumor cells stimulate osteoclasts and, along with the tumor cells’ response to the calcium in the extracellular fluid of the bone, cause osteolytic lesions (holes in the bone) and thus destruction of the bone itself. Some tumors cause mineral release from the bone, which wears away, resulting in a matrix resorption that leaves holes in the bone. Some tumors release osteoclastic-stimulating factors that cause bone weakness. Tumor cells can also secrete chemicals that cause the build up of abnormal bone, called osteosclerotic bone.
Repair of bone is a unique form of healing involving two processes—intramembranous ossification and endochondral ossification—both of which contribute to successful repair. Intramembranous ossification begins in the mesenchyme, where an ingrowth of capillaries aids in the differentiation of mesenchymal cells into osteoblasts, which lay down the organic matrix of bone. This results in the formation of an early callus. In endochondral ossification, bone formation occurs in the primary and secondary centers of the bone, creating a stabilization process that is seen in displaced bones or unstable bones, such as fractured ribs. Table 37-1 presents the specific stages of fracture repair.
| Stage | Time Frame | Characteristics |
|---|---|---|
| Inflammation | Begins after the initial injury and lasts until cartilage and bone begin to form a few days to several months later | Swelling and pain |
| Soft callus | Begins when pain and swelling decrease; may last 3 weeks to months | Bone fragments are united by fibrocartilage or fiberbone, and a soft callus forms. This is the point of clinical stability. |
| Hard callus | Begins after a soft callus forms and lasts 3 to 6 months after fracture | After the soft callus is initially stable, it is converted to bone. This corresponds to clinical and radiologic union. |
| Remodeling | Begins after clinical and radiologic union and may last years | Bone structure, including the medullary canal, is restored to normal. Primary cortical healing is an extremely slow process, estimated to progress 1 mm every 3 weeks. |
Pain is a primary symptom of bone metastasis. It is caused by tumor enlargement, perilesional edema, increased intraosseous pressure, or weakness from bone loss. Direct pressure stimulates the release of pain mediators, such as prostaglandins, bradykinins, and histamine. Tumor invasion causes activation of mechanoreceptors and nociceptors, which leads to the development of pain.
Clinically I have found that patients are extremely accurate about feeling bone metastasis and pinpointing its site, even before its presence is confirmed by diagnostic tests.
EPIDEMIOLOGY AND ETIOLOGY
Bone is the third most common site for metastasis after the lungs and liver. The incidence of pathologic fracture is approximately 2%. Up to 70% of newly diagnosed patients with cancer develop bone metastasis, and of these approximately 20% develop a pathologic fracture that requires surgical intervention (Wedin, 2001; Townsend et al., 1994). Interventions to treat bone metastases include radiotherapy (Hartsell et al., 2005), radioisotopes, surgery, hormone therapy, chemotherapy (Struthers et al., 1998), and bisphosphonates (Table 37-2).
| Generic Name | Trade Name | Uses | Reference |
|---|---|---|---|
| Clodronic acid | Clodronate | Breast, prostate cancers | Gulley & Dahut, 2005 |
| Ibandronate sodium | Boniva | Postmenopausal osteoporosis | Coleman, 2005 |
| Pamidronate disodium | Aredia | Breast, myeloma cancers and hypercalcemia | Coleman, 2005 |
| Zoledronic acid | Zometa | Breast, myeloma, prostate, lung, and solid tumor cancers | Kohno et al., 2005; Hirsh et al., 2004 |
Prevention of pathologic fractures is superior to treatment after the fracture occurs. In general, breast cancer metastases that are purely lytic are more likely to fracture than those that are blastic or mixed; 18.5% of pathologic fractures from breast cancer occur in the humerus (Flemming & Beales, 1986). After reconstruction of the humerus, fracture occurs as a complication in about 40% of these patients, with a mean bone union time of 12 months (Rose et al., 2005). Blastic lesions in the proximal femur have a high rate of fracture. Pathologic fractures are associated with a significant increase in the risk of death, especially for pateints’ with breast cancer and multiple myeloma (Saad et al., 2007).
RISK PROFILE
Risk factors include the type of cancer, type of treatment, size of the lesion, location of the lesion, whether the lesion is lytic or blastic, symptoms associated with the lesion, environmental safety, and co-morbidities (e.g., diabetes, malnutrition, alcoholism). Overall the common metastatic sites are the femur and then the humerus. Other sites are the tibia and the ulna, and vertebral compression also is common.
• Cancer types include primary bone cancers (Ewing’s, malignant fibrous histiocytoma, osteosarcoma) and metastatic cancers of the breast, prostate, lung, thyroid, renal cell, bowel, pancreas, rectum, and ovary, myeloma, lymphoma and, in rare cases, vulvar cancer (Marcocci et al., 1989).
• In patients with breast cancer, a metastatic lesion 2.5 cm or larger in the femoral cortex or anywhere in the body that is accompanied by pain requires fixation and treatment to prevent fractures (Parrish & Murray, 1970; Snell & Beals, 1964).
• Treatment of prostate cancer with androgen deprivation therapy (Malcolm et al., 2007), LHRH agonists, orchiectomy, and/or radiation therapy increases the fracture rate by 9% (Townsend et al, 1997).
• Lytic lesions a have a higher fracture incidence (Mirels, 2003), because they reduce both the strength and stiffness of the bone. Lung cancer metastasis is typically a lytic lesion in bones below the elbow and knee. Because patient survival is short, these painful lesions usually are treated with radiation or surgery.
• Thyroid cancer has a long survival time, and these patients require lifetime follow-up for possible fractures.
• Renal cell metastasis to bone occurs in about 25% to 50% of patients.
• Radiation therapy to the bone increases the risk of fracture by up to 41%. This is theorized to be due to failure of reossification or to softening of the bone.
• Women over 55 years of age with sarcoma who have radiation doses of 60 Gy or higher have an increased risk of pathologic fractures (Holt et al., 2005).
• In patients with sarcoma, more than 50% of fractures occur in the distal femur and 25% in the proximal femur (Ebeid et al., 2005).
• Unsafe environments, such as clutter, throw rugs, loose edges on floors, uneven floors, and icy pavements, can lead to fractures. Children with bone metastasis are vulnerable to fractures associated with falls while running or playing.
PROGNOSIS
The prognosis depends on the underlying disease process. The quality of the bone proximal and distal to the fracture site must be adequate to support fixation. Internal fixation with postoperative radiation has been found to afford the best prognosis (Perez et al., 1972). Complete pathologic fracture and soft tissue metastasis are negative prognostic variables for 1-year survival in patients with breast cancer, with 11% requiring reoperation for repair of pathologic fractures (Wedin, 2001). The 5-year event-free survival rate is 60% in patients with nonmetastatic extremity osteosarcoma, but it drops to 17% with recurrence (Bacci et al., 2006). Predictors of survival for patients who undergo surgery for treatment of bone metastasis include the diagnosis, clinical estimation of survival, hemoglobin count, number of visceral metastases, and ECOG performance score (Nathan et al., 2005). Administration of zoledronic acid (Zometa) prolonged the median survival time in patients with lung cancer and other solid tumor by 2.5 months (Hirsh et al., 2004).
PROFESSIONAL ASSESSMENT CRITERIA (PAC)
2. Hallmark symptoms include sharp pain initially, then dull pain that increases with movement, as well as limited range of motion.
3. Assess the wound site (if applicable): Color, temperature, sensation distal to area, ability to bear weight; also patient anxiety, apprehension.
4. Assess vital signs for indicators of pain: Increased heart rate, blood pressure, and respiratory rate. Fever indicates an inflammatory process or tumor growth.
5. Rib fractures lead to restricted breathing (assess respiratory rate and excursion) and pain (assess severity on a 1 to 10 scale).
6. Assess patient’s mobility and ability to perform ADLs.
7. Assess serum calcium levels for an increase that indicates bone disease.
8. Assess the patient for depression.
9. Assess total Gy of radiation received; if 60 Gy or greater, the patient is at increased risk for pathologic fractures.
NURSING CARE AND TREATMENT
1. Immobilize the limb and avoid lifting or movement of the affected area.
2. Initiate pain control (e.g., large doses of corticosteroids [dexamethasone 20-100 mg IV for epidural tumor]; analgesics; radiation; chemotherapy; nerve blocks; radiopharmaceutical agents; bisphosphonates [see Table 37-2]; calcitonin; surgical intervention for fixation of fracture site). Reassess pain every 1 to 2 hours.
3. Diagnostics: Bone scan to detect bone metastasis and to assess overall extent of disease except in myeloma, renal cell, and thyroid cancers, for which skeletal x-ray films are used. Note that bone scans do not provide detail of the structural lesion in the bone. PET scans are very sensitive to metastatic diseases and are often used as comparison studies throughout the patient’s life. MRI (superior to myelography) (Kent & Larson, 1988) is superior in detecting epidural tumors and has great accuracy for differentiating pathologic fractures from stress fractures (Fayad et al., 2005). CT scans are often prescribed, especially before a biopsy.
4. Initiate treatment:
• Pamidronate for patients with multiple myeloma.
• Zoledronic acid (Zometa), a bisphosphonate that is a potent inhibitor of osteoclast-mediated bone resorption, to reduce the risk of bone complications (Kohno et al., 2004; Saad et al., 2004; Rosen et al., 2001) in patients with breast cancer, prostate cancer (Saad et al., 2006), myeloma, lung cancer, and other solid tumors. May cause osteonecrosis of the jaw (Lipton, 2007).
• Radioisotopes (e.g., strontium-89 and samarium-153) in patients with prostate metastasis.
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