AAOS Orthopedic Basic Science MCQs (Part 4): Bone Physiology & Pharmacology | 2026 Board Review

Osteopenia, decreased bone mass without fracture risk as defined by the WHO criteria for diagnosis of osteoporosis, is when a woman's T-score is within -1 to -2.5 SD. The T-score represents a comparison to young normals or optimum peak density. The Z-score represents a comparison of BMD to age-matched normals. Measurements of bone mineral density (BMD) at various skeletal sites help in predicting fracture risk. Hip BMD best predicts fracture of the hip, as well as fractures at other sites.

Gentamycin and the aminoglycosides (ie, streptomycin, tobramycin, amikacin, and neomycin) work by binding to the 30s ribosome subunit, leading to the misreading of mRNA. This misreading results in the synthesis of abnormal peptides that accumulate intracellularly and eventually lead to cell death. These antibiotics are bactericidal. Cephalosporins, vancomycin, and penicillins interfere with cell wall synthesis by inhibiting the transpeptidase enzyme. Polymyxin, nystatin, and amphotericin increase cell membrane permeability by disrupting the functional integrity of the cell membrane. The quinolones inhibit the enzyme, DNA gyrase. Lastly, metronidazole forms oxygen radicals that are toxic to anaerobic organisms because they lack the protective enzymes, superoxide dismutase and catalase.

A muscle that lengthens as it is activated is an eccentric contraction. Isometric contraction involves no change in length. Concentric contraction occurs while the muscle is shortening. In isotonic contraction, the force remains constant through the contraction range. Isokinetic muscle contraction occurs at a constant rate of angular change of the involved joint. Garrett WE, Speer KP, Kirkendall DT (eds): Principles & Practice of Orthopaedic Sports Medicine. Philadelphia, PA, Lippincott Williams & Wilkins, 2000, pp 12-13.

Osteoclasts originate from the monocyte/macrophage lineage. Fibroblasts and osteoprogenitor cells originate from mesenchymal stem cells and do not form osteoclasts. Plasma cells reside in the bone marrow and are derivatives of the hematopoietic system. Megakaryocytes are also in the bone marrow and synthesize platelets. Zaidi M, Blair HC, Moonga BS, et al: Osteoclastogenesis, bone resorption, and osteoclast-based therapeutics. J Bone Miner Res 2003;18:599-609. Brinker MR: Bone (Section 1), in Miller M (ed): Review of Orthopaedics, ed 2. Philadelphia, PA, WB Saunders, 1996, pp 1-35.

Power analysis is used to determine the minimum number of specimens (sample size) such that, if a difference is found that is large enough to be clinically important, the associated level of statistical reliability will be high enough (ie, the P-value will be small enough) for the investigators to conclude that the difference observed in the study also holds in general. For the statistician to do a power analysis, the investigators must first decide on the minimum difference that they consider to be clinically important, for example, a reduction of 3% in the rate of infection. It is important to recognize that the choice of what constitutes the minimum difference in the rate of infection that is clinically (ie, medically) important cannot and should not be done by the statistician. Rather, this is a clinical-medical issue and must be done by the physician researcher based on a comprehensive assessment of the medical risks and benefits. The power analysis also requires an estimate of the variance in the data, which may be based on previous similar studies, if available. A statistician can then calculate the minimum sample size (number of patients) required such that, if a clinically important difference does, in fact, exist between the full populations, there is a reasonable probability or power (typically 80% to 90%) that a difference this large also will occur between the sample populations at the desired level of statistical significance (usually, but not necessarily, P < 0.05). The other answers refer to types of analyses that are usually conducted after the data are collected.

In most orthopaedic applications, the materials are strong enough to withstand a single cycle of loading in vivo. However, these loads may be large enough to initiate a small crack in the implant that can grow slowly over thousands or millions of cycles, eventually leading to gross failure. Such fatigue failure has occurred with virtually every type of implant, including stainless steel fracture plates and screws, bone cement in joint arthroplasty, and polyethylene inserts in total knee arthroplasty. Lewis G: Fatigue testing and performance of acrylic bone-cement materials: State-of-the-art review. J Biomed Mater Res Br 2003;66:457-486. Stolk J, Verdonschot N, Huiskes R: Stair climbing is more detrimental to the cement in hip replacement than walking. Clin Orthop 2002;405:294-305.

Intradiskal pressure is lowest when the patient is in the supine position. Sitting is associated with higher intradiskal pressures than standing. Flexion also increases intradiskal pressure. The combination of flexion and sitting produces the highest intradiskal pressure. Nachemson and Morris found that intradiskal pressure increases as position changes from lying supine, lying prone, standing, leaning forward, sitting, and sitting leaning forward. Twisting or straining in positions of relatively high intradiskal pressure may predispose patients to herniation of the intervertebral disk. Patients with a herniated disk may also notice their pain worsens with activities that increase the disk pressure, including the positions mentioned, or activities that increase intra-abdominal pressure (coughing, sneezing, straining). Nachemson A, Morris JM: In vivo measurements of intradiscal pressure. J Bone Joint Surg Am 1964;46:1077-1092.

Answering this question requires understanding of two important biomechanics concepts. First, because neither the object being held in the hand nor the body is moving and, hence, their accelerations are zero, the problem is one of static equilibrium in which the sum of the moments acting on the body is zero. Second, a moment is the action of a force that causes an object to rotate about any point away from its line of action. The magnitude of the moment is the magnitude of the force multiplied by the perpendicular distance between the line of action and the point (often called the moment arm or lever arm). In this problem, two forces are causing moments about the elbow. The magnitude of the moment caused by the object in the hand is 5 N times 30 cm or 150 N-cm. To maintain equilibrium, the moment caused by the biceps force must also have a magnitude of 150 N-cm. Its moment arm is 2 cm, so the magnitude of the biceps force is 150 N-cm divided by 2 cm, which equals 75 N. In general, functional loads such as the object are always at a mechanical advantage (ie, have a longer moment arm) over the muscle. Therefore, muscles must generate large forces to overcome the moments caused by even small functional loads. An KN, Chao ES, Kaufman KR: Analysis of muscle and joint loads, in Mow VC, Hayes WC (eds): Basic Orthopaedic Biomechanics, ed 2. New York, NY, Lippincott-Raven, 1997, pp 1-14.

The notochord is the anatomic structure that defines the phylum Chordata. The notochord plays a fundamental role in the development of the skeleton, and it exists only for a short period of time. During its temporary existence, the notochord serves as a transient axis of support, provides for the initial axis of orientation of the developing embryo, and most importantly, plays a vital role in the induction of the tissues that eventually form the vertebral column.

Osteoarticular allografts are devoid of host chondrocytes but do contain "mummified" cellular debris left over from donor processing. The cartilage architecture is preserved in the first 2 to 3 years after transplantation. The articular surface is covered with a pannus of fibrocartilage maintaining the joint space radiographically; this pannus later contains islands of fibrocartilage containing host mesenchymal stem cells. Degenerative changes to the joint surface occur earlier and are more severe in joints that are unstable. Only with degenerative changes at the surface is there histologic evidence of subchondral revascularization. Often degenerative changes involving the articular cartilage reach the tidemark, but the tidemark itself remains structurally intact. Enneking WF, Campanacci DA: Retrieved human allografts: A clinicopathological study. J Bone Joint Surg Am 2001;83:971-986.

The amount of deformation resulting in response to an applied load depends on the stress distribution that the load creates in the structure and the stress versus strain behavior of the material that makes up the structure. Axial and bending loads create stress distributions that involve normal stresses and normal strains. Although all five responses are indeed material properties, only one, elastic modulus, relates normal stresses to normal strains. In fact, axial and bending stiffness are directly proportional to modulus, so that a nail made from stainless steel will have nearly twice the stiffness of a nail made from titanium alloy (because their respective elastic moduli differ by about a factor of two). Hayes WC, Bouxsein ML: Analysis of muscle and joint loads, in Mow VC, Hayes WC (eds): Basic Orthopaedic Biomechanics, ed 2. New York, NY, Lippincott-Raven, 1997, pp 74-82. Buckwalter JA, Einhorn TA, Simon SR (eds): Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 159-165.

Older individuals ingest less Vitamin D and are unable to generate as much as younger people via the skin in response to ultraviolet exposure; thus, there is a decrease in the levels of serum 25(OH) D. This reduction in 25(OH)D leads to a reduction in calcium absorption. There is also decreased conversion in the kidney of 25(OH)D to 1,25(OH)D. This all leads to an increase in the daily requirements of both calcium and Vitamin D. It also results in a responsive increase in PTH secretion in the elderly, as well as renal function impairment and possible renal resistance to PTH. Dawson-Hughes B, Harris SS, Krall EA, et al: Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age and older. N Engl J Med 1997;337:670-676. Recker RR, Hinders S, Davies M, et al: Correcting calcium nutritional deficiency prevents spine fractures in elderly women. J Bone Miner Res 1996;11:1961-1966.

Bone destruction is primarily mediated by osteoclastic bone resorption, and cancer cells stimulate the formation and activation of osteoclasts next to metastatic foci. Increasing evidence suggests that receptor activator of NF-kB ligand (RANKL) is the ultimate extracellular mediator that stimulates osteoclast differentiation into mature osteoclasts. In contrast, OPG inhibits osteoclast development. IL-8 but not IL-5 is known to play a role in osteoclastogenesis. MMP-2 and collagen type I do not have a direct role in osteoclastogenesis. Kitazawa S, Kitazawa R: RANK ligand is a prerequisite for cancer-associated osteolytic lesions. J Pathol 2002;198:228-236.

Synovial tissue is composed of vascularized connective tissue that lacks a basement membrane. Two cell types (type A and type B) are present: type B cells produce synovial fluid. Synovial fluid is made of hyaluronic acid and lubricin, proteinases,and collagenases. It is an ultrafiltrate of blood plasma added to fluid produced by the synovial membrane. It does not contain erythrocytes, clotting factors, or hemoglobin. It lubricates articular cartilage and provides nourishment via diffusion. Synovial fluid exhibits non-Newtonian flow characteristics. The viscosity coefficient is not a constant, the fluid is not linearly viscous, and its viscosity increases as the shear rate decreases.

The collagen orientation changes from parallel in the superficial zone to a more random pattern in the middle zone and finally to perpendicular in the calcified zone. Koval KJ (ed): Orthopaedic Knowledge Update 7. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 498-499.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to increase the risk of pseudarthrosis. In a controlled rabbit study, nonunions were reported with the use of toradol and indomethacin. NSAIDs are commonly used medications with the potential to diminish osteogenesis. Studies clearly have demonstrated inhibition of spinal fusion following the postoperative administration of several NSAIDs, including ibuprofen. Cigarette smoking is another potent inhibitor of spinal fusion. Glassman SD, Rose SM, Dimar JR, et al: The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Spine 1998;23:834-838.

Radiographic fusion success rates are best described as slightly rather than substantially improved. Hospital stay and time to fusion also are not substantially decreased. Use of BMP does eliminate the need for autograft harvest for anterior lumbar interbody fusion/cage. The need for postoperative bracing is not altered based on graft choice. Early studies of posterolateral fusion applications appear to show a greater potential benefit of rhBMP-2 over autograft. Not all BMP formulations perform the same with regard to safety and effectiveness. Other osteoinductive proteins in clinical trials (BMP-7, GDF-5) will require individual analysis of these properties.

Cell activation and transcription varies with the target cell, the growth factor-receptor combination, and the biologic state of the cell. The growth factors in the transforming growth factor-beta (TGF-ß) superfamily signal through serine/threonine kinase receptors. Fibroblast growth factors, insulin-like growth factors, and platelet-derived growth factors signal through tyrosine kinase receptors. Growth hormone is released by the pituitary and circulates to the liver where target cells are stimulated to release insulin-like growth factor. Lieberman J, Daluiski A, Einhorn TA: The role of growth factors in the repair of bone: Biology and clinical applications. J Bone Joint Surg Am 2002;84:1032-1044.

Degenerative spondylolisthesis at L3-4 is the most likely diagnosis. This spondylolisthesis would result in foraminal stenosis affecting the third lumbar root and leading to anterior thigh and knee pain and hip flexor weakness. L4-5 spondylolisthesis would impinge on the L4 root in the foramen. Degenerative disk disease without hypertrophy is unlikely to have root impingement. Posterolateral herniations typically affect the inferior root and are less common in this age group. Hoppenfeld S: Physical Examination of the Spine and Extremities. Upper Saddle River, NJ, Prentice Hall, 1976, p 250.

It has been proposed that an imbalance in the proteolytic cascade involving matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may play a role in the development or progression of malignancy. TIMP activity has been shown to be weak or nonexistent and MMP activity to be high in patients with soft-tissue sarcoma. The level of vascular endothelial growth factor is shown to be a negative prognostic indicator because the expression of this factor is associated with angiogenesis and aggressive growth of many tumors including Ewing' s sarcoma and chondrosarcoma. Stromelysin is a type of MMP. The biology of cytokines in malignancy is complex. A low level of interleukin-1 is not known to be associated with high-grade tumors.

Passive glycation of articular cartilage occurs over decades. One of the consequences of this glycation appears to be the stiffening of collagen. This phenomenon appears to be associated with an increased collagen degradation and development of osteoarthrosis. Passive glycation also results in a relatively yellow appearance. Passive glycation does not directly influence chondrocyte proliferation. DeGroot J, Verzijl N, Wenting-van Wijk MJ, et al: Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis. Arthritis Rheum 2004;50:1207-1215.

The results are statistically significant (at the arbitrary level of P < 0.05). That is, they indicate a probability of only 1/10,000 that the observation that the drug is effective in reducing healing time by 0.3 weeks occurred by chance selection of the study subjects. However, because the statistical power of a study increases with the number of subjects included (sample size), a difference that is trivial clinically can occur with a very high level of statistical significance (a very small P-value) if enough patients are included in the study. Because of this, the P-value alone, no matter how small, does not establish clinical significance or importance. Rather, the clinical significance of the observed difference must be assessed taking into consideration the medical importance of the difference if it is, in fact, true in the general population. In this example, the reduction in healing time of only a few days is probably clinically unimportant, particularly if the use of the new growth factor is expensive, complex, and/or has substantial side effects.

The basic diagnostic test for hepatitis C (HCV) is detection of an antibody to epitopes on an enzyme-linked immunosorbent anti-HCV assay (ELISA). The currently used ELISA has high sensitivity (92%) and specificity (95%). False positives, however, still occur. The currently used supplemental test for HCV is strip immunoblot assay, which is based on detection of several HCV epitopes on nitrocellulose paper by antibody-capture techniques. Molecular amplification by PCR technology is very sensitive, but difficult to standardize and susceptible to contamination. Microarray and proteomics are relatively recent molecular techniques used for analysis of genes or proteins, respectively. A Northern blot is used to detect mRNA levels of specific genes but is not used in this situation. de Medina M, Schiff ER: Hepatitis C: Diagnostic assays. Semin Liver Dis 1995;15:33-40.

Maffucci's syndrome is a form of enchondromatosis associated with subcutaneous and deep hemangiomas. Similar to Ollier's disease, the risk of malignant transformation of the enchondromas is much higher than that of a solitary enchondroma. Multifocal nonossifying fibromas associated with other clinical findings such as mental retardation and café-au-lait spots is known as Jaffe-Campanacci syndrome. There are two types of multifocal forms of histiocytosis: Letterer-Siwe and Hand-Schüller-Christian disease. Schwartz HS, Zimmerman NB, Simon MA, et al: The malignant potential of enchondromatosis. J Bone Joint Surg Am 1987;69:269-274. Frassica F: Orthopaedic pathology, in Miller M (ed): Review of Orthopaedics, ed 2. Philadelphia, PA, WB Saunders, 1996, pp 292-335.

Joint contact pressure is a stress and as such is defined as the load transferred across the joint divided by the contact area between the joint surfaces (the area over which the joint load is distributed). Therefore, any mechanism that decreases the load across the joint (eg, a walking aid) will decrease the stress. Similarly, any mechanism that increases the area over which the load is distributed (eg, using a more conforming set of articular surfaces in a knee joint arthroplasty) will also decrease the stress. Other mechanisms that influence joint contact pressure include the elastic modulus of the materials (cartilage in the case of natural joints and polyethylene in joint arthroplasty) and the thickness of the structures through which the joint loads pass. Bartel DL, Bicknell VL, Wright TM: The effect of conformity, thickness, and material on stresses in UHMWPE components for total joint replacement. J Bone Joint Surg Am 1986;68:1041-1051.