2.7 Metastatic bone disease

Bone is the commonest site for metastasis in cancer and is of particular clinical importance in breast and prostate cancers because of the prevalence of these diseases. At postmortem examination, 70% of these patients have evidence of metastatic bone disease. However, bone metastases may complicate a wide range of malignancies, resulting in considerable morbidity and complex demands on healthcare resources. Carcinomas of the thyroid, kidney, and bronchus also commonly give rise to bone metastases, with an incidence at postmortem examination of 30–40%. However, tumours of the gastrointestinal tract rarely (less than 10%) produce bone metastases.

This is typically in one of three modes:

Bone metastases are the most common cause of cancer-related pain. The pathophysiological mechanisms of pain in patients with bone metastases are poorly understood but probably include tumour-induced osteolysis, tumour production of growth factors and cytokines, direct infiltration of nerves, stimulation of ion channels, and local tissue production of endothelins and nerve growth factors. Although 80% of patients with advanced breast cancer develop osteolytic bone metastases, approximately two-thirds of such sites are painless.

Different sites of bone metastases are associated with distinct clinical pain syndromes. Common sites of metastatic involvement associated with pain are the base of the skull (in association with cranial nerve palsies, neuralgias, and headache), vertebral metastases (producing neck and back pain with or without neurologic complications secondary to epidural extension), and pelvic and femoral lesions (producing pain in the back and lower limbs, often associated with mechanical instability).

Hypercalcaemia most often occurs in those patients with squamous cell lung cancer, breast and kidney cancers, and certain haematological malignancies (in particular myeloma and lymphoma). In most cases, hypercalcaemia is a result of bone destruction, and osteolytic metastases are present in 80% of cases.

Secretion of humoral and paracrine factors by tumour cells stimulates osteoclast activity and proliferation, and there is a marked increase in markers of bone turnover. Several studies have established the role of parathyroid hormone-related peptide in most cases of malignant hypercalcaemia.

The signs and symptoms of hypercalcaemia are non-specific, and the clinician should have a high index of suspicion. Common symptoms include fatigue, anorexia, and constipation. If untreated, a progressive increase in serum calcium level results in deterioration of renal function and mental status. Death ultimately results from renal failure and cardiac arrhythmias.

The destruction of bone by metastatic disease reduces its load-bearing capabilities and results initially in microfractures, which cause pain. Subsequently, fractures occur (most commonly in ribs and vertebrae). It is the fracture of a long bone or the epidural extension of tumour into the spine that causes the greatest disability.

Spinal cord compression is a medical emergency, and suspected cases require urgent evaluation and treatment. Pain occurs in most patients, is localized to the area overlying the tumour, and often worsens with activities that increase intradural pressure (e.g. coughing, sneezing, or straining). The pain is usually worse at night, which is the opposite pattern of pain from degenerative disease. There may also be radicular pain radiating down a limb or around the chest or upper abdomen. Local pain usually precedes radicular pain and may predate the appearance of other neurologic signs by weeks or months. Most patients with spinal cord compression will have weakness or paralysis. Late sensory changes include numbness and anaesthesia distal to the level of involvement. Urinary retention, incontinence, and impotence are usually late manifestations of cord compression. However, lesions at the level of the conus medullaris can present with early autonomic dysfunction of the bladder, rectum, and genitalia.

Back pain is a frequent symptom in patients with advanced cancer and in 10% of cases is due to spinal instability. The pain, which can be severe, is mechanical in origin, and frequently patients are only comfortable when lying still.

The role of the orthopaedic surgeon in the management of metastatic bone disease, always part of a multidisciplinary team, falls into three principal categories (British Orthopaedic Association Guidelines):

Any surgical procedure should provide immediate stability, allowing weight bearing and as a general rule the fixation should aim to last the lifetime of the patient. The surgeon must assume that the fracture may not unite and should aim to stabilize all lesions in the affected bone. Furthermore, if there is the slightest doubt as to the underlying pathology, and in particular where there is a solitary bony lesion, then further investigations including scintigraphy, magnetic resonance imaging scan of the lesion, and percutaneous bone biopsy should be carried out before definitive surgery. This allows the detection of primary bone neoplasms or solitary renal metastases (these have good prognosis and should be treated like primary bone tumours)

Where fracture is likely to occur, then prophylactic fixation should be performed prior to the administration of radiotherapy. It is essential, therefore, to have a reliable method of predicting the risk of a pathological fracture occurring.

In an effort to provide a reliable and reproducible measure of the risk of pathological fracture, Mirels devised a scoring system which is a useful aid to fracture risk assessment (Table 2.7.1). For scores of eight or above, the risk of fracture is high and prophylactic fixation should be carried out prior to radiotherapy being administered.

Where destruction is limited to the femoral neck or head, a cemented hemiarthroplasty or total joint replacement is recommended as a primary procedure. Long stem femoral implants should be considered. Subtrochanteric fractures or lesions with limited bone loss are best stabilized by ‘reconstruction’ nails with locking screws up the femoral neck (Figure 2.7.1). This greatly reduces the risk of subsequent femoral neck fracture.

The majority of pelvic lesions are treated with prophylactic palliative radiotherapy alone. However, acetabular reconstruction with pins and cement can be carried out where there is an imminent risk of failure of the socket

Metastatic lesions or fractures of the scapula and clavicle are usually managed with radiotherapy alone. In the humeral head, significant destruction is, in most cases, best treated by hemiarthroplasty.

Intramedullary nailing is the procedure of choice with locking screws to give rotational stability and to prevent telescoping (Figure 2.7.2). Apart from the case of solitary renal metastases, the potential spread of tumour cells within the medulla by nailing is acceptable within the context of palliative treatment. The entire bone and operative site should be included in the postoperative radiotherapy field. Since these fractures are unlikely to unite, load-bearing, rather than load-sharing, devices should be used, and solid nails, of a greater diameter than may be used for purely traumatic fractures, may be considered. Packing of major bone defects with methylmethacrylate bone cement is useful in maintaining stability in some cases. All of the lesions in the affected bone should be stabilized to minimize the risk of further surgery being required. Reconstruction nails, stabilizing the femoral neck, are recommended in the femur.

Extensive bone destruction at the metaphyses of major long bones is sometimes so great that reconstruction can only be achieved using custom or modular endoprostheses (Figure 2.7.3). However, major surgery such as this has to be balanced against the likely timeframe of survivorship of the patient.

Radiotherapy is generally palliative, and often given as a single fraction. It can produce effective bone healing and sclerosis and, when given prophylactically, can prevent pathological fracture occurring. It will not, however, cure pain of a ‘mechanical’ nature, and only 30–40% of pathological fractures will unite even after radiotherapy. It is recommended that following nailing or other surgical procedures in patients with metastatic bone disease, radiotherapy to the affected bone and operative field (unless field sizes are excessive) should be considered by the appropriate specialist within the context of the multidisciplinary team. The spinal cord is radiosensitive, and this may limit the scope for adjuvant treatment of the axial skeleton.

Endocrine therapy, bisphosphonates, and chemotherapy may all have a role in the management of patients with metastatic bone disease.

Over the last two decades there has been considerable improvement in the implants available to manage structural deficiency of the spine, notably pedicle screws, cages, and plating or rodding systems. The objectives of surgery are:

Treatment of spinal metastatic disease may involve radiotherapy ± surgery:

The prognosis for patients with metastatic bone disease is steadily improving. The orthopaedic surgeon should never assume that a lytic lesion, particularly if solitary, is a metastasis and appropriate tests should always be done to exclude a primary bone neoplasm. Management of metastatic bone disease should always be done in the context of a multidisciplinary team.