There are 206 bones in a normal adult classified in 3 general categories: long bones, short bones, and flat bones. These bones interact via connective tissue elements to form the skeleton, which is further divided into the axial skeleton (skull, rib cage, and vertebral column) and the appendicular skeleton (limbs, shoulder girdle, and pelvic girdle).¹

Bone development occurs in two ways: endochondral or intramembranous ossification. Endochondral ossification occurs primarily in long and short bones such that chondrocytes form a cartilaginous model and osteoblasts and osteoclasts remodel this to mature lamellar bone.² Endochondral ossification of long bones eventually gives rise to three anatomic zones referred to as the epiphysis, metaphysis, and diaphysis (Figure 1-1). Intramembranous ossification occurs primarily in flat bones such that immature bone is formed without a cartilaginous model and is subsequently remodeled into mature, lamellar bone.¹

The entire bone is covered by periosteum. Beneath the periosteum are three layers of bone, the most superficial of which is cortical. Underneath the cortical bone lies the cancellous bone,
which surrounds the medullary cavity (Figure 1-1). The periosteum is an innervated and highly vascularized dense connective tissue. Cortical (compact) bone forms the bone’s exterior and comprises up to 80% of the skeleton. Its fundamental functional unit is the osteon or Haversian system. The osteon is a series of concentric layers of mineralized matrix surrounding a central canal (Haversian canal), which provides a tract for vascular and nerve supply. Each concentric layer contains a ring of spaces called lacunae that house the osteocyte cell responsible for maintaining bone homeostasis. Cancellous (trabecular or spongy) bone has a less organized, trabecular structure with a higher surface area to mass ratio than cortical bone and is predominantly found at the end of long bones. It is highly vascularized, less dense, weaker, and more elastic than cortical bone. Normal cortical and cancellous bone is referred to as lamellar bone and is stress oriented in configuration. This composite nature of bone gives rise to its viscoelastic property such that its strain is time dependent when undergoing deformation. Lastly, the innermost medullary cavity is the site of hematopoietic stem cell differentiation.¹

Bone is a dynamic tissue that consists of a mineralized organic matrix that is highly regulated by its cellular components. Osteoblasts act to synthesize and deposit the organic component of bone matrix called osteoid, which consists predominantly of type 1 collagen. Osteoid is eventually mineralized to hydroxyapatite consisting predominantly of calcium and phosphate. Osteoclasts act to break down bone in a process called bone resorption. Resorption occurs with osteoclasts tightly clinging onto the bone surface and secreting acids to dissolve the mineral matrix along with collagenases and other enzymes to break down the organic components. It is essential to maintain homeostasis between osteoclast and osteoblast activity.

Osteoblasts are key regulators of this balance because they act to modulate osteoclast activity. For example, in response to hypocalcemia, the parathyroid gland will release parathyroid hormone (PTH) to increase serum calcium levels chiefly through bone resorption. PTH receptors, however, are located on osteoblasts,
which will subsequently act to differentiate and activate osteoclast precursors for resorption when stimulated. This is mediated by osteoblast surface expression of the extracellular membrane protein RANKL (Receptor Activator of Nuclear factor-Kappa B Ligand). Osteoclast precursor cells contain RANK receptors on their membranes that allow them to differentiate into mature osteoclast cells capable of resorption when bound to RANKL (Figure 1-2). Osteoclast precursor cells contain RANK receptors on their membranes that allow them to differentiate into mature osteoclast cells capable of resorption. Osteoblasts additionally secrete osteoprotegerin, which acts to bind RANKL and prevents its interaction with the RANK receptor and prevents osteoclast differentiation when necessary for homeostatic control. It is, therefore, the ratio of secreted osteoprotegerin to RANKL expression by osteoblasts that dictates the degree of bone resorption. PTH is one of many factors that induce osteoclast activation.¹

Healthy bone is constantly being remodeled by osteoblast and osteoclast activity. Wolff’s law states that this remodeling occurs in response to mechanical stress in order to adapt to these loads. Thus, an increase in mechanical stress will increase bone deposition, whereas the lack of mechanical stress results in bone loss. For
example, owing to the lack of a gravitational stress, astronauts are prone to bone loss in space.¹

Skeletal muscle is one of the three types of muscle found in the body and is responsible for voluntary movement. The skeletal muscle cell, or fiber, is multinucleate and cylindrical in shape with a plasma membrane referred to as the sarcolemma. Each fiber contains a plethora of myofibrils, which are most importantly composed of actin, myosin, and titin. These myofibrils are systematically arranged into thick and thin filaments, which are further organized into a series of repeating sections called the sarcomere across the entire length of the myofibril (Figure 1-3). It is this pattern that gives skeletal
muscle a striated appearance under a microscope. There are two types of muscle fibers: type 1, or slow twitch, and type 2, or fast twitch, fibers. Type 1 fibers are responsible for sustained contraction and, therefore, allow for endurance activities. Type 2 fibers have a faster contraction rate for a shorter duration than type 1 fibers and, therefore, produce more force at any contraction velocity.¹

Skeletal muscle contraction occurs by the process of excitation-contraction coupling. This begins with acetylcholine release in the neuromuscular junction by a motor neuron with subsequent depolarization of the motor end plate. In response to this depolarization, voltage-gated calcium receptors on the sarcolemma undergo a conformational change which, due to direct mechanical linkage with the underlying sarcoplasmic reticulum receptor, causes a sharp release of calcium from the sarcoplasmic reticulum and subsequent muscle contraction via the sliding filament theory. According to this theory, the released calcium allows the thin actin filaments to be pulled by the thick myosin filaments in an adenosine tri-phosphate (ATP)-dependent cross-bridge cycling process that causes the filaments to slide along each other, resulting in sarcomere shortening and contraction. One axon can depolarize many myofibers called a motor unit. Motor units are recruited from smallest to largest for efficient contraction.¹

The cross-sectional area of a healthy skeletal muscle is proportional to its capacity to generate a contractile force. The contraction velocity of muscle is a function of its fiber length. There are three main types of muscular contraction:

Isokinetic contraction: The total energy expenditure of the muscle remains constant while muscular length changes. Isotonic and isokinetic contractions are a measure of dynamic strength, whereas isometric contractions are a measure of static
strength.¹ These contractions are balanced by agonist and antagonist muscle groups that, although functionally oppose each other’s actions, are necessary for proper movement and tension generation.³

Macroscopically, skeletal muscle has two junctions: a myotendinous junction and a bone-tendon junction. A myotendinous junction occurs where muscle transitions to tendon with continuous collagen fibers linking the two. A bone-tendon junction, or enthesis, refers to the tendons insertion to bone, which can be direct or indirect. Muscular strains and tears most often occur at the myotendinous junction because the maximum stress occurs here during an eccentric contraction, where the internal force is less than the external force.¹

A joint refers to the space and connections made between the bones of the body that typically allow for relative movement. Joints are predominantly either diarthroses or synarthroses. Diarthroses, or synovial joints, allow for movement between bones, whereas synarthroses do not. The synovial joint can be further categorized by the type of movement it permits. The six groups in this categorization are a plane joint, ball and socket joint, hinge joint, pivot joint, condyloid joint, and saddle joint.⁴

The typical synovial joint consists of a synovial cavity between bones that is filled with synovial fluid and encased in a fibrous joint capsule. The articular surface is the boney end that is covered with approximately 2 to 4 mm of hyaline cartilage. Hyaline cartilage is composed of approximately 75% water, 15% type II collage, 10% proteoglycans, and 1% to 5% chondrocytes by mass. Hyaline cartilage is biphasic as it has both fluid and solid properties that function in load bearing.² Consequently, it functions to decrease the friction between the boney surfaces as well as to distribute the load. It further acts as a shock absorber by offloading compressive and shear forces at the joint surfaces. The absence of a direct neural and blood supply to articular cartilage limits its capacity to heal or regenerate. It is nourished by diffusion from two sources: synovial fluid and, to a lesser degree, through vessels within the subchondral bone. The lone
cells of cartilage, chondrocytes, are mechanically stimulated and act to produce and maintain the integrity of the extracellular matrix.¹

Further involved in friction reduction, shock absorption, and force offloading at the level of the joint is the viscous synovial fluid consisting primarily of hyaluronic acid. The synovial fluid is produced and maintained by the inner membrane layer of the joint capsule, referred to as the synovial membrane. There are two cell types in this layer: fibroblast synovial cells, which secrete the synovial fluid, and macrophage-like synovial cells, which impart limited immunity to the joint space. The outer joint capsule membrane, or fibrous membrane, is an avascular white fibrous tissue functioning to maintain the overall stability and alignment of the joint. Further adding to stability are extracapsular and intracapsular ligaments that articulate the ends of the bones and tendons inserting around the joint area to allow for movement of the joint.¹

OA is the most common arthritis and refers to age- or trauma-related degeneration of the articular cartilage with bone remodeling and formation. This nonuniform degeneration results in decreased shock absorption as well as increased frictional forces acting across the chondral surfaces of the joint, potentially exposing bone. As such, there will be secondary inflammation resulting in pain, stiffness, and swelling of the joint. Large weight-bearing joints, such as the knee and hip, are more commonly affected though any joint can be affected. Risk factors include advanced age, such that there is
X-ray evidence in at least 80% of people over the age of 55, female sex (2:1 to 3:1), obesity, history of trauma, and occupation (construction work, etc).⁴ Age-related wear and tear OA without any other attributable causes is called primary, or idiopathic, OA. If a specific etiology can be attributed to the development of OA, it is considered secondary OA.

Patients will most commonly present with joint pain and swelling along with possible crepitus, decreased range of motion (ROM), and boney enlargement of the knee. They will often complain of morning stiffness that lasts less than 30 minutes as well as activity-associated pain that is relieved with rest. Labs such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are typically within normal limits and are obtained to rule out any other possible etiologies. The hallmark radiograph findings of OA include decreased joint space, osteophytes, cysts, and subchondral sclerosis (Figure 1-4).
Synovial fluid is noninflammatory with a WBC <2,000 per mm³. The prognosis is dependent on the etiology, affected joint, and state of the articular cartilage.⁴ The state of articular cartilage can be classified using either the Modified Outerbridge or the International Cartilage Repair Society grading scales. Both are graded from I to IV and stratify based on the thickness of the cartilage defect along with the exposure of subchondral bone (Table 1-1).¹

Treatment is dependent on severity and extent of degeneration. Initial management should include weight loss along with physical therapy and exercise programs to strengthen the stabilizing muscles of the affected joint. First-line pharmacologic management in the form of nonsteroidal anti-inflammatory drugs (NSAIDs) for pain and inflammation with acetaminophen for pain as needed are then to be used.⁴ Intra-articular joint injection can further be used in the event that pharmacologic management is not enough. Glucocorticoid
(steroid) with lidocaine injections is used to potently reduce the inflammation along with providing pain relief. These injections should be limited to no more than three to four times a year because overuse can accelerate joint degeneration. Hyaluronate injections are another option. These synthetic injections mimic synovial fluid and can restore some function and stability with subsequent pain control. If all of these measures fail to control the patient’s pain and restore function, then surgery in the form of chondral transplants or joint replacement is indicated. If the patient is unable or not agreeable to surgery, then they should be referred to pain management.⁵