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Pathologic Fractures in Children
Introduction
Pathologic fractures occur in diseased bone, and, in children, such fractures are caused by a spectrum of conditions different from those in adults. Children’s diseases frequently associated with pathologic fractures include noncancerous benign bone tumors and congenital or genetic abnormalities affecting the skeleton. Polyostotic disease with fractures affecting the immature skeleton is often caused by osteomyelitis, histiocytosis, vascular neoplasms, and metastases (neuroblastoma and Wilms tumor). Rarely, sarcomas may initially present with a fracture, and these patients require special consideration in their treatment approach. In contrast, causes of pathologic fractures in the adult skeleton, especially in individuals older than 40 years, include malignancies such as myeloma, metastatic carcinoma, lymphoma, and, rarely, sarcomas of the bone. Occasionally, giant cell tumors and enchondromas are identified. Elderly individuals frequently are seen with pathologic fractures from osteoporosis or Paget disease in addition to metastasis ( Table 4.1 ).
Table 4.1
Age Distribution of Common Orthopedic Bone Tumors
| Tumor | ||
|---|---|---|
| Age (Years) | Benign | Malignant |
| 0–5 | Chondroma Unicameral bone cyst Osteoid osteoma Nonossifying fibroma Fibrous dysplasia |
Neuroblastoma (metastatic) Rhabdomyosarcoma (metastatic) Ewing sarcoma Osteosarcoma Lymphoma |
| 10–40 | Chondroma Osteoid osteoma Aneurysmal bone cyst Unicameral bone cyst Nonossifying fibroma Fibrous dysplasia Eosinophilic granuloma Chondroblastoma (skeletally immature) Giant cell tumor (skeletally mature) |
Osteosarcoma Ewing sarcoma Lymphoma |
| 40+ | Chondroma Giant cell tumor Hemangioma |
Carcinoma Multiple myeloma Lymphoma Chondrosarcoma Osteosarcoma Chordoma |
The axial skeleton is frequently the site of metastatic foci because of its rich vascular supply relative to the appendicular skeleton. In general, pathologic fractures create a broad differential diagnosis. As a result, the orthopedic oncologist must approach each case by considering the patient’s age, symptoms, image appearance, and an understanding of bone biology. Algorithms rarely suffice in pediatric orthopedics or orthopedic oncology.
The goal of this chapter is to introduce the reader to the multitude of variables involved in the successful treatment of pediatric pathologic fractures. A diagnosis must be made before embarking on any treatment strategy. Tissue documentation by biopsy is highly recommended to confirm the underlying diagnosis that lead to the pathologic fracture. Depending on the confidence of the treating surgeon, a radiographic diagnosis may substitute for a tissue one, for example, in unicameral bone cysts (UBCs). After these variables are carefully weighed and balanced, an optimal treatment strategy can be formulated for a particular child. A different child with the same fracture may benefit from a different treatment. Individually, pediatric orthopedics and orthopedic oncology each require a high degree of cognitive decision making. Pediatric pathologic fractures present an intersection of the two, which makes this decision making all the more complex.
Bone Physiology
Bone is a specialized connective tissue with matrix consisting predominantly of type I collagen. It is a dynamic organ that receives one-fifth of the cardiac output and is one of the only organs capable of true regeneration. Shaping of the skeleton and the buildup of bone mass during childhood and adolescence are a result of the constant interplay between bone formation and bone resorption. Bone remodeling continues throughout life. The average individual reaches peak bone mass in the third decade of life, and the adult skeleton contains approximately 2 million bone-remodeling units. Each unit comprises a spatial and temporal group of organized cells responsible for osteoclastic bone resorption and osteoblastic bone formation in response to local and environmental stimuli.
Bone resorption is mediated by the osteoclast, a multinucleated giant cell derived from granulocyte-macrophage precursors. Bone formation requires the presence and function of the osteoblast, which is derived from mesenchymal fibroblast-like cells. Net bone formation occurs by the process of coupling (contiguous and concurrent bone formation and resorption). Under normal circumstances, 88% to 95% of the bone surface area is quiescent, while the remainder is involved in active remodeling. The total time required to complete a remodeling cycle for a typical bone-remodeling unit in a young adult is estimated to be 200 days. One bone-remodeling unit takes approximately 3 weeks to complete bone resorption, whereas it takes 3 months to form bone in an adult. Bone formation is quicker in children. When this balance of resorption and formation is disordered by a pathologic process, the integrity of bone can be compromised.
Bone strength is related to a combination of material and structural properties. The mineral component of bone is responsible for most of its compressive strength, whereas both mineral and protein components are important for strength in tension. Normal activity results in forces of compression, tension, and torsion. However, bone is weakest in torsion, and even a small cortical defect can significantly reduce torsional strength. For example, a 6-mm drill hole in the tibial shaft cortex, such as that generated to obtain a bone biopsy specimen, reduces torsional strength by 50%.
Pathologic Fracture
A tumor present at a fracture delays, alters, or prevents bone healing. In certain instances, the rapid growth of the tumor cells overwhelms the reparative process of bone. In metastatic bone disease, damage to the skeleton is usually much more extensive than can be expected simply from the number of malignant cells present. Much evidence has now shown that most of the tumor-induced skeletal destruction is mediated by osteoclasts. Malignant cells secrete factors that both directly and indirectly stimulate osteoclastic activity. These factors include a variety of cytokines: interleukin-1 (IL-1), IL-6, tumor necrosis factor, IL-11, IL-13, and IL-17. IL-1 is the most powerful stimulator of bone resorption in vitro. Growth factors identified in tumorous bone include transforming growth factor α, transforming growth factor β, and epidermal growth factor. Paracrine factors that also stimulate osteoclastic activity include prostaglandin E and parathyroid hormone–related protein (PTHrP), and these factors are typically produced by malignant cells. PTHrP is immunologically distinct from parathyroid hormone and stimulates osteoblasts and stromal cells to secrete the receptor activator of nuclear factor kB ligand (RANK-L). RANK-L is one of the mechanisms by which osteoblast and osteoclast function is physiologically linked. It binds to osteoclast precursors, leading to osteoclastogenesis and subsequently bone resorption. Because of RANK-L induction by cancer cells, osteoclast activity is elevated leading to resorptive phenomena, like the osteolysis induced by metastatic breast cancer and the hypercalcemia of lung cancer. RANK-L production in bone has also been shown to promote cancer cell migration to the local environment, thus creating a positive feedback loop for bone metastases.
What is a pathologic fracture? Is it a radiologic, clinical, or combination diagnosis? Must the bone be completely or incompletely broken or displaced (or both) in one or more planes? Must the patient have symptoms or pain with activity? Can the bone be microscopically but not macroscopically fractured? These questions are pertinent because their answers are vital to the formation of proper treatment strategies. For the purposes of discussion, a pathologic fracture is defined as a clinically symptomatic interruption in the cortex of a diseased bone—displaced or not. Although fractures are typically macroscopic, they do not necessarily have to be so. A child’s bone is much more plastic than that of an adult. Bending without complete fiber separation occurs in a child and may be clinically relevant.
Healing of pathologic fractures has been found to correlate most closely with tumor type and patient survival. Resection of the tumor deposit is an important part of the management of pathologic fractures. Thus, the biology of the bone and its biomechanics in conjunction with tumor pathology are important contributing variables to understand when the overall treatment of pathologic fractures is planned.
The most important task to be performed when a pathologic fracture is first detected is to establish the diagnosis with certainty. Although a radiographic diagnosis can be accurate, especially for UBCs, it is not a substitute for a tissue-confirmed diagnosis. Consequently, the authors recommend that a biopsy be strongly considered for all initial pathologic manifestations and other neoplasms of bone. Biopsy is a complex cognitive skill that depends on a careful history, physical examination, and interpretation of radiographic staging studies, including proper assessment of local, regional, and distant disease. It is crucial to determine whether polyostotic bone involvement is present. The surgeon is best able to interpret the diagnostic, anatomic, and pathologic significance of musculoskeletal disease and should thus review the images personally.
Biopsies are best performed by individuals with frequent experience. Complications from an improperly selected biopsy site can be devastating. Nondiagnostic or nonrepresentative harvesting of lesional tissue delays the diagnosis, and biopsy performed before complete imaging can hamper treatment planning. Care must be taken when choosing image-guided biopsy versus open biopsy, as harm and delay can occur with a seemingly innocuous core/needle biopsy. Only after a tissue diagnosis is made can proper treatment ensue. Treatment must be based on understanding of three key components in each case. The surgeon must understand the relevant bone biology and physiology (component 1) and how this is affected by the pathologic diagnosis obtained (component 2) in order to determine how best to restore function (component 3).
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