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  • Bony metastases are more common than primary bone tumours, which are relatively rare. 
  • Survival of patients with metastatic disease has increased significantly in recent years –particularly in breast and prostate cancer. 
  • In the UK alone there are approximately 9000 women with skeletal metastases from breast cancer, of which over 20% will survive more than 5 years. 
  • Bone is the third most common site of metastatic disease. 

Cancers most likely to metastasise to bone: 

  • Breast
  • Lung
  • Prostate
  • Thyroid
  • Kidney
  • Bowel 
  • Carcinomas are much more likely to metastasise to bone than sarcomas. 
  • The axial skeleton is seeded more than the appendicular skeleton, partly due to the predominance of red bone marrow in the former. 
  • The ribs, pelvis, proximal femur and spine are commonly affected. 
  • Batson’s vertebral venous plexus allows cells to enter the vertebral circulation without first passing through the lungs. The sluggish blood flow in this plexus is more conducive to tumour survival, accounting for the high rate of prostate cancer metastasis to the spine. 
  • Metastatic bone lesions can be described as osteolytic, osteoblastic, and mixed. 
  • Osteolytic lesions are most common where the destructive processes outstrip the laying down of new bone (breast/lung/thyroid/renal cancer). 
  • Osteoblastic lesions result from new bone growth that is stimulated by tumour cells via tumour-secreted endothelin 1 (prostate cancer).

Pain

  • Pain is a major source of morbidity with bone metastasis. 
  • It is the most common symptom found in 70% of patients, caused by: 
    • Stretching of the periosteum by the tumour. 
    • Nerve stimulation in the endosteum. 
    • Pathological fractures.

Pathological fracture 

  • Pathological fractures are most common in breast cancer due to the lytic nature of the lesions. They are uncommon in lung cancer due to short life span, and rare in prostate cancer where osteoblastic lesions predominate.
  • Lytic bone metastases must be greater than 1 cm and have destroyed 30–50% of the bone density in order to be seen on radiographs.

Hypercalcaemia

  • Osteoclast activity is up regulated via the RANK, RANKL, and osteoprotegrin pathway. This results in a higher rate of bone resorption, releasing calcium into the systemic blood circulation.
  • Symptoms of hypercalcaemia can be summarised by the classic mneumonic: “bones, stones, thrones, abdominal groans, and psychiatric overtones.” Respectively, these refer to: bone pain/muscle weakness, kidney stones, polyuria (and polydipsia), abdominal pain/nausea/vomiting, depression/confusion.
  • If untreated, hypercalcaemia can lead to coma and death.

Other symptoms

  • Spinal metastases can cause spinal cord compression resulting in neurological deficit.

Known primary

  • Bone sScan – will show areas of metastases earlier than plain radiographs. Used to determine the extent of spread.
  • CT- of chest, abdomen, and pelvis.
  • Bloods- FBC, Bone biochemistry, U&Es, LFTs, boagulation screen.
  • Biopsy is not necessary as the primary cancer is already known so the result will not affect treatment.

Unknown primary

  • The priorities are to investigate the lesion in order to determine and treat the primary, and to differentiate it from a primary bone lesion.
  • Bloods – FBC, bone biochemistry, U&Es, LFTs, coagulation screen, ESR, CRP. 
  • Serum and urine protein electrophoresis to rule out multiple myeloma.
  • Other blood tests: tumour markers such as PSA (prostate cancer), calcitonin (thyroid cancer), CA 15-3 (breast cancer).
  • Bone scan. 
  • Plain radiographs of the affected limb(s) (make sure the whole bone is scanned, not just the section where the lesion is).
  • CT of the affected bone(s), chest, abdomen and pelvis.
  • Biopsy lesion(s) for histology (where clusters of epithelial cells are seen in metastatic lesions) and microbiology (incl. TB). Different tissue stains can help aid diagnosis such as CK7 in breast cancer.
  • Normally palliative although solitary metastases, particularly renal, can do very well.

Radiotherapy

  • Useful for reducing bone pain and progression of tumour growth. 
    • 90% of patients will receive some relief.
    • 50% will receive near complete relief with between 20 to 40.5 gray of radiation.
  • Complications: radiation induced osteonecrosis and theoretically may increase rate of stress fracture or non-union.
  • Lesions that do not represent a risk for fracture may be treated with radiation or by appropriate chemotherapy directed at the tumour. 
  • Patients who have recurrence of pain because of biomechanical weakness should be managed with operative stabilisation. 

Biphosphonates

  • Downregulate bone resorption and therefore reduce pain and the risk of fracture. Studies have also demonstrated and a reduction of hypercalcaemia.
  • Although bisphosphonates act quickly to reduce hypercalcaemia, long-term administration is necessary to treat widespread osteolytic disease. 
  • Clodronate can be administered intravenously or orally, and although it affects bone resorption it does not alter bone mineralisation: 
    • In several studies, clodronate was found to reduce bone pain after a few months of therapy.
    • The need for palliative radiation therapy; and, potentially, the risk of pathological fracture was also reduced with clodronate. 

Hormone therapy

  • Appropriate to use in breast cancer in which the tumour cells have certain receptors (oestrogen, progesterone, HER2). Expression of these receptors needs to be confirmed on histological analysis before treatment as not all tumours express receptors.

Pathological fracture

  • Prophylaxis is MUCH easier than treating an already fractured lesion.
  • Pathological fractures have been reported to occur in 9–29% of patients who have bone metastases, depending on the location of the lesion. 
  • High risk of pathological fracture: 
    • >50% loss of the cortex/shaft diameter on any view. 
    • Avulsion of the lesser trochanter is an indication of imminent hip fracture.
    • A lesion 2.5 cm or greater
    • Mirels’ scoring system (Clin Orthop Relat Res 1989, see below) – a numerical score is assigned to four variables: the location of the lesion, the degree of pain, the radiographic appearance, and the size of the lesion. Mirels recommended irradiation and observation of lesions with a score of 7 points or less, and operative treatment of those with a score of 8 points or more. 
  • In patients with vascular tumours such as those of renal or thyroid cancer, embolisation should be done before surgery.

Role of the surgeon

  • Prevent a pathological fracture through prophylactic fixation. 
  • Stabilise or reconstruct the bone after fracture. 
  • Decompress spinal cord and nerve roots if these are compressed.
  • Confirm diagnosis if in doubt: 
    • Whenever there is the slightest doubt about the diagnosis biopsy is MANDATORY. The prophylactic nailing of a lesion that turns out to be a primary is a disaster that may put at least the patient’s limb in jeapordy by spreading tumour down the cavity and can even put the patient’s life at risk through systemic dissemination. 

Goals of surgery

  • Relief of pain. 
  • Restoration of the ability to mobilise. 
  • Preserve stability and function. 
  • Increase survival. 
  • Improved fracture healing.

Surgical principles

  • Load bearing is preferred to load sharing. 
  • Defects can be filled with cement.
  • Following nailing the whole bone needs to be included in the radiotherapy field. 
  • Plate fixation is acceptable in the upper limb with or without cement augmentation. 
  • Fractures around the hip need careful consideration: 
    • Usually hip hemiathroplasty or total hip replacement (THR). 
    • Extensive destruction of the proximal femur may require endoprosthetic replacement. 
    • Acetabular lesions should be reconstructed. 

Surgical options

  • Intramedullary nails – used for diaphyseal fractures (entire bone must be included in postoperative radiotherapy). 
  • Prosthesis – epiphyseal fractures. 
  • Endoprosthetic replacement– extensive epiphyseal/metaphyseal lesions. 
  • Major bone defects can be filled by methylmethacrylate cement. 
  • Emergency surgery is done for spinal metastasis in the hope of preserving neurological function. 
  • Postoperative radiotherapy should be considered in all cases, once initial wound healing has occurred.

These are well established although clinical evidence suggests that they are still sometimes ignored. Load-bearing, rather than load-sharing, devices are preferred and in the diaphysis of long bones, intramedullary nailing is the procedure of choice with locking screws used when appropriate and major bone defects filled by methylmethacrylate. Apart from a solitary renal metastasis, the spread of tumour cells within the medulla by nailing is acceptable, but the entire bone should subsequently be included in postoperative radiotherapy. In the upper limb, particularly in the forearm where stresses are relatively low, plate fixation and augmentation with cement can be highly effective.

The management of fractures about the hip differs significantly from that of purely traumatic injuries. Speed of surgery is less important than preoperative planning and a full medical and radiological assessment should be made initially. There is no virtue in undue delay but these patients are almost always haemodynamically stable, and have not been subject to significant trauma. They can be nursed comfortably on bed rest or traction for several days while appropriate investigations are carried out. When destruction is limited to the femoral neck or head, a cemented hemi-arthroplasty or total joint replacement is recommended as a primary procedure. Devices such as the dynamic hip screw are rarely indicated as they have a high rate of failure. Radiographs of the entire femur must be obtained before operation to exclude more distant disease as far as possible and long-stemmed implants may be used to reduce the risk of subprosthetic fracture. Extensive proximal femoral destruction is only treatable by endoprosthetic replacement, while periacetabular lesions should be reconstructed using threaded rods, reinforcement rings, bone cement and other techniques, as described by Harrington.6Patients with a life expectancy of less than six weeks rarely gain useful benefit from major reconstructive surgery, but the decision regarding any individual case must be taken by the breast-care team. 

Postoperative radiotherapy should be considered in all cases, once initial wound healing has occurred. 

If there is the slightest doubt as to the nature of the pathology, and in particular when there is a solitary bony lesion, further investigations including scintigraphy, MRI and percutaneous bone biopsy should be carried out before definitive surgery. Nailing of a lesion of a long bone which proves to be a primary bone tumour is a disaster, spreading tumour cells throughout the marrow cavity, and often precluding limb-salvage surgery. Patients with a solitary renal metastasis have a good prognosis if the lesion is treated as a primary neoplasm. Referral to a regional centre is recommended.

Prompt and appropriate surgical management of bony metastases is highly cost-effective, although controlled prospective trials to demonstrate this are difficult to construct, and probably unethical. The cost of surgery and of specialised implants is recovered within days if previously immobile patients can mobilise, or dependent patients become able to care for themselves. Inadequate orthopaedic treatment often leads to a need for costly revision surgery with increased suffering and potential complications.

The mechanism for delivery of an effective service for the orthopaedic management of bony metastases need not be complex or costly. At least one orthopaedic surgeon within each trauma team should be identified as the “lead clinician” with responsibility for metastatic disease of the appendicular skeleton. The organisation of spinal services should also be addressed locally. Patients admitted to hospital with actual or imminent pathological fractures should be reviewed by that clinician or team during the next working day and a plan of management agreed. Complex cases, those involving a possible primary sarcoma, or requiring endoprosthetic, acetabular or custom surgery, need to be discussed with the supraregional orthopaedic oncology centre since concentration of experience improves clinical outcomes. 

The lead clinician should take part in a weekly multidisciplinary clinical conference with the breast surgeon, medical oncologist, radiologist and other relevant personnel to review cases for which surgical intervention may be indicated. Combined clinics or parallel clinics may also be considered if the workload is sufficient. These are not essential, however, and may not always be an effective use of clinical time. 

Purchasers of health care should require clear evidence that an appropriate strategy for the management of these patients is in place when allocating contracts for both trauma and cancer services, in order to provide a high-quality and timely service in line with the principles of the Calman–Hine Report. Orthopaedic surgery has much to offer cancer patients in terms of quality, and sometimes quantity of life. It is hoped that the recommendations of the working party will be widely debated among orthopaedic surgeons, and if they are acted upon a significant contribution to cancer services will have been made.

  • Metastatic disease in long bones: A proposed scoring system for diagnosing impending pathologic fractures.

Mirels H. Department of Orthopaedics, University of the Witwatersrand, Johannesburg, South Africa. Clin Orthop Relat Res 1989 Dec; (249): 256–264 

 

  • The role of the orthopaedic surgeon in metastatic disease of the appendicular skeleton. Working Party on Metastatic Bone Disease in Breast Cancer in the UK. 

Roger M. Tillman. J Bone Joint Surg [Br] 1999; 81(1): 1–2. 

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References

  • 1. O’Donoghue DS, Howell A, Walls J. Orthopaedic management of structurally significant bone destruction in breast cancer metastases. J Bone Joint Surg [Br] 1997; 79-B: Suppl I: 98.
  • 2. BASO. Guidelines for the management of metastatic bone disease in breast cancer in the UK. Europ J Surg Oncol 1999: in press.
  • 3. Fidler MW. Incidence of fracture through metastases in long bones. Acta Orthop Scand 1981; 52: 623–627.
  • 4. Mirels H. Metastatic disease in long bones: a proposed scoring system for diagnosing impending pathological fracture. Clin Orthop 1989; 249: 256.
  • 5. Aaron AD. Current concepts review: treatment of metastatic adenocarcinoma of the pelvis and the extremities. J Bone Joint Surg [Am] 1997; 79-A: 917–932.
  • 6. Harrington KD. Orthopaedic management of extremity and pelvic lesions. Clin Orthop 1995; 312: 136–147.