Skeletal Disorders

Leonard Rosenthall and Peter MacDonald Introduction

The course of treatment for bone pain and skeletal abnormalities is effected by an accurate diagnosis of the problem. Nuclear medicine has a role to play in both the investigation of the problem and, in some cases, the treatment of bone and joint disorders.

Skeletal Anatomy and Physiology

In the long bones of adults, blood primarily enters the diaphyseal cortex by flowing outwards from the medulla rather than inwards from periosteal vessels. The nutrient artery divides in the medullary cavity and anastomoses with the epiphyseal and metaphyseal arteries which are direct branches of the regional systemic vessels and enter through the numerous foramina penetrating the bones near their ends. Blood flow from the epiphyseal and metaphyseal arteries is quantitatively greater than that of the nutrient artery supply to the diaphysis. Periosteal arteries are part of the network supplying the surrounding muscles. About two-thirds to three-fourths of the inner cortex is sustained by the medullary arterial network. An obstructed nutrient artery can result in a compensatory increase in centripetal periosteal flow to support the full thickness of the cortex through interconnecting channels. Flat bones, such as the cranium, and non-articular segments of short bones are supplied by numerous periosteal vessels which nourish the cortex, cancellous bone and medulla.

The three main cells in bone are osteoclasts, osteoblasts and osteocytes. Osteoblasts evolve from bone marrow-derived, pluripotent, stromal stem cells. Their role is to form and mineralize bone matrix, and to synthesize skeletal growth factors. The ultimate fate of the osteoblasts has not been clearly defined. Some are buried within the bone matrix as osteocytes, while others become lining cells which cover quiescent bone surfaces. Osteocytes are connected to each other and the lining cells through a canalicular network that contains the bone's extracellular fluid. They are believed to release chemical messengers in response to physical strains in order to initiate the appropriate modelling or remodelling response to mechanical stimuli. Osteoclasts are derived from the hematopoietic precursors of the monocyte-macrophage lineage and function in the bone resorption process. They are formed by the fusion of mononuclear cells and are characterized as large multinucleated cells with a ruffled border.

Technical Considerations


Bone imaging is achieved with 99mTc-labelled phosphate and diphosphonate complexes (collectively referred to as radiophosphate). The most commonly used

Nuclear Medicine, edited by William D. Leslie and I. David Greenberg. ©2003 Landes Bioscience.

agent is 99mTc-labelled methylene diphosphonate (MDP). Uptake in bone is dependent on blood flow and extraction efficiency. As the vascularity increases, it is associated with an increase of the bone-seeking tracer in the extracellular fluid, which accumulates by passive diffusion. Tracer is then selectively concentrated by the reactive bone. The relationship between blood flow and tracer uptake is not linear. A point is reached when the uptake remains constant despite blood flow increase, indicating a diffusion-limited process.

The site of deposition of the radiophosphate complex has been fairly well established. Evidence from in vivo microautography indicates that 99mTc-phosphate is adsorbed preferentially onto the mineral phase of forming bone, and that this adsorption occurrs preferentially onto amorphous calcium phosphate before it matures into hydroxyapatite crystal. It has also been shown by chemical separation of mineral and matrix in a rat bone repair model that with the intravenous delivery of a double label, 99mTc-MD-32P, there was preferential binding of 99mTc to the organic matrix while MD-32P bound to the mineral phase. The deduction from these observations was that 99mTc-MDP is taken up by bone and then dissociates, allowing 99mTc to concentrate in newly formed matrix whereas the MDP moiety remains attached to the mineral phase. The preceding explains why uptake of bone tracer correlates with osteoblastic activity, since these areas are rich in unmineralized osteoid matrix and immature calcium phosphate.

Imaging Procedure

For imaging with 99mTc-MDP, a dose of about 740 MBq (20 mCi) is administered intravenously. Static scintigraphy is performed about 2-3 hours later, a time when normal urinary excretion has lowered the soft tissue background to acceptable levels. The procedure is modified for three-phase bone imaging i.e., sequential nuclear blood flow, blood pool and delayed static images. With the gamma camera head positioned over the area of interest, the radiotracer is injected as a bolus and immediately thereafter serial 3- or 5-second images are obtained for about 60 seconds to complete the blood flow phase. Within 5 minutes of the blood flow study a static blood pool image is taken. Three hours later, whole body or spot images, or both are obtained (Fig. 1).

In cellulitis, diffuse increased uptake occurs in the blood flow and blood pool phases, while it is normal or diffuse, but less intense because of a regional hyperemia, in the delayed phase. Acute osteomyelitis, for example, is characterized by a focal increased concentration in all three phases.


Bone trauma can present as frank fractures, which are obvious by radiography, or occult fractures wherein plain radiography is not diagnostic. Fatigue (stress) fractures occur in normal bone, while insufficiency (fragility) fractures (Fig. 2) occur with osteoporosis. Other causes of bone injury are growth plate injuries, avulsion fractures, dislocations, shin splints, bone bruising and enthesopathy (where tendon attaches to bone).

The healing process in most fractures is triggered within hours of the insult. A procallus forms and at 24 hours buds of granulation tissue have already penetrated the hematoma at the fracture site. This leads to eventual lysis of the hematoma and

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