Rickets/Ca+/Vit D
S/S Curve
Material Properties*
Bisphosphonates
Statistics
100
Low serum phosphate and normal calcium levels are found in what common etiology of hereditary rickets?
X-linked hypophosphatemic rickets is the most common form of hereditary rickets. It is an X-linked dominant disorder which has been linked to the PHEX gene. Laboratory findings of this disorder include low serum phosphate, normal serum calcium and 25 hydroxycholecalciferol levels, and inappropriately low 1,25-dihydroxyvitamin D3. Carpenter et al. showed hypophosphatemic rickets was initially referred to as “vitamin D resistant rickets” due to its lack of response to therapeutic vitamin D. Current treatment with activated vitamin D metabolites (calcitriol or alfacalcidol) and phosphate salts have been shown to help with this condition. Illustration A shows an insufficiency fracture of the proximal tibia in an adult patient with X-linked hypophosphatemic rickets. A stress fracture on the medial tibia may be a presenting feature of untreated disease. Incorrect Answers: Answer 2: Vitamin D-dependent rickets, type I, is a rare autosomal recessive disorder. Answer 3: Vitamin D-dependent rickets, type II, is a rare autosomal recessive disorder, most often caused by mutations in the vitamin D receptor gene. Answer 4: Autosomal dominant hypophosphatemic results from a rare mutation in the fibroblast growth factor 23 (FGF23) gene. Answer 5: Jansen's metaphyseal chondrodysplasia is a skeletal dysplasia that results from ligand-independent activation of the type 1 parathyroid hormone receptor (PTHR1).
100
Define the stress at which a material begins to undergo plastic deformation?
1. Toughness 2. Ultimate strength 3. Yield strength 4. Fatigue strength 5. Endurance limit PREFERRED RESPONSE ▼ 3 A material undergoing plastic deformation will not return to its original form once the stress is removed. This occurs once a material has been subject to stress past the yield strength, also called the yield point. Prior to the yield point, elastic deformation occurs, and the material will return to its original form once the stress is removed. Illustration A demonstrates these definitions in the classic stress-strain curve. The amount of energy a material can absorb before failure is defined as toughness. Ultimate strength is the highest point on the stress-strain curve. It represents the maximum stress a material can absorb while being stretched before "necking", when the cross-sectional area of the material begins to contract. Fatigue strength refers to cyclic testing of a material. Also called fatigue limit or endurance limit, it is the amount of cyclic stress that can be applied to a material before failure. Endurance limit has also been used to define the maximum level of stress that can be applied to a material cyclically and never cause failure.
100
A new composite material is being evaluated fo r potential use as a prosthetic ligament. In measuring the tensile strength of this material, why is it important to consider and accurately control the loading rate?
1. Ligaments are viscoelastic. 2. Ligaments are elastic. 3. Ligaments experience creep. 4. Ligaments undergo stress relaxation. 5. Strain in ligaments is recoverable. PREFERRED RESPONSE: 1 DISCUSSION: Ligaments are viscoelastic, meaning that their deformation under load depends not only on the magnitude of the load but also on the rate of loading. Un der higher load rates (faster loading), natural ligaments are stiffe r and stronger. Therefore, it is important in such an experiment to apply a loading rate that is physiologically relevant, ie, that represents typical or worst case activities. Creep refers to deformation of a viscoelastic material over time under constant load. Stress relaxation refers to a decrease in stress over time under a constant displacement.
100
Two major phannacologic classes of bisphosphonates exist: nitrogen-containing and non-nitrogencontaining compounds. The nitrogen-containing compounds work by which of the fo llowing actions?
PREFERRED RESPONSE: 3 DISCUSSION: Bisphosphonates represent the most clinically important class of anti resorptive agents available to treat diseases characterized by osteoclast-mediated bone resorption. Two classes of bisphosphonates exist: nitrogen-containing and non-nitrogen-containing compounds. The non-nitrogencontaining bisphosphonates work by metabolizing into cytotoxic AT P analogs. The nitrogen-containing bisphosphonates work via the mevalonate pathway by inhibiting GTPase fo rmation, leading to loss of GTP prenylation and eventual induction of osteoclast apoptosis.
100
The ability of a study to detect the difference between two interventions if one in fact exists describes which of the following?
The study power is defined as the ability of a study to detect the difference between two interventions if one in fact exists. The power of a statistical test is correlated to the magnitude of the treatment effect, the designated type I (alpha) and type II (beta) error rates, and the sample size n. The power is equal to (1-beta) whereby beta is the false negative rate. Kocher et al. present a Level 5 review of epidemiology and biostatistics. The review discusses study design, hypothesis testing, diagnostic performance, measures of effect, outcomes assessment, evidence-based medicine, and biostatistics. They discuss that in the orthopaedic literature power is typically set at 80%, (leaving a 20% chance that the study will display no significant association when there is an actual association.)
200
You are seeing a 4-year-old girl with Rickets on a mission trip to Haiti. What laboratory studies would help confirm a nutritional deficiency as opposed to an X-linked genetic disorder as a cause of her condition? ___PTH ____Alk Phosp _____Phosphate
The key laboratory factor that differentiates nutritional from hypophosphatemic rickets is an elevated PTH. Tortolani et al. review the differential diagnosis of bone mineral density deficiency in their JAAOS review. As discussed, nutritional rickets shows low to normal serum calcium, low serum phosphate, elevated alkaline phosphatase, and elevated parathyroid hormone. While nutritional rickets is due to dietary deficiency, hypophosphatemic rickets is caused by the inability of kidney proximal tubules to reabsorb phosphate due to mutated PHEX gene, found on the X chromosome. PHEX is thought to protect extracellular matrix glycoproteins from proteolysis. Hypophosphatemic rickets shares many clinical manifestations with nutritional rickets, but shows PTH levels that are not elevated, even with calcium and phosphate abnormalities (pseudohypoparathyroidism). Loeffler and Sherman evaluated the addition of phosphate to the standard vitamin D therapy in hypophosphatemic rickets on long-term growth and deformity correction. They found no additional benefit of this therapy and as such, it is currently not recommended. Ferris et al. review their treatment of 19 patients with hypophosphatemic rickets and found that staged surgical intervention afforded better results but these patients, even with intervention, developed early degenerative joint disease.
200
A surgeon desires to use an implant that will be able to absorb as much energy as possible before it fa ils. The implant should be made of a material that has which of the following properties?
1. A high modulus of elasticity 2. A low modulus of elasticity 3. High intrinsic toughness 4. A high yield stress 5. Brittleness PREFERRED RESPONSE: 3 DISCUSSION: High intrinsic toughness is defined as the amount of energy per volume a material can absorb without breaking. A high modulus of elasticity and a low modulus of elasticity are incorrect because the modulus of elasticity refers to the stiffness of the materiaL A brittle material absorbs little energy before breaking. High yield stress is incorrect because it is only one of several factors that lead to a high toughness. While the yield stress is the point at which plastic deformation begins, if coupled with a brittle material, the energy absorbed would be low relative to a ductile materiaL
200
What description best describes galvanic corrosion?
1. corrosion resulting from an electrochemical potential created between two metals in conductive medium 2. corrosion resulting from contact sites between materials under load 3. corrosion resulting from oxygen tension differences 4. corrosion from localized pits on metal surfaces 5. corrosion from allergic reaction PREFERRED RESPONSE ▼ 1 There are many modes of corrosion in orthopaedic implants and galvanic corrosion is a type of corrosion which results from an electrochemical potential created between two metals in a conductive medium. This is often seen at the interface of metals (e.g plates and screws) when different metals are used. The conductive medium is usually serum or interstitial fluid. Answer 2 describes fretting corrosion and answer 3 describes crevice corrosion. Answer 4 describes pitting corrosion and answer 5 does not make sense.
200
What effect do bisphosphonate medications have on spinal fusion surgery when taken in the postoperative period?
Bisphosphonates (e.g. alendronate) are used to treat osteoporosis. The mechanism of action is inhibiting the formation of the ruffled border of osteoclasts, resulting in decreasing bone turnover. Huang et al performed a rat study comparing alendronate to placebo and found that fusion rates were lower in those treated with alendronate. However, the fusion masses were larger in the alendronate treated rats despite lower fusion rates (why #4 is incorrect). Lehman et al in another placebo controlled rate study found that the fusion rates for placebo (76%) were greater than the alendronate group (45%). Alendronate works on osteoclasts and does not affect calcium directly. Taking calcium should have no effect on alendronate (why #1 is incorrect). At this time there are no formal recommendations of when to stop bisphosphonate medication prior to spinal fusion surgery.
200
The range within which it is probable that the true value lies for the whole population is defined as?
What is : CONFIDENCE INTERVAL When an unknown value is sought, the confidence interval gives the statistician a set of parameters within which the “true” value is located. The confidence interval is used to indicate the reliability of an estimate. The standard deviation is a quantity calculated to indicate the extent of deviation for a group as a whole. The mode is the value which occurs most frequently in a given set of data. The variance is a quantity equal to the square of the standard deviation. The incidence is the frequency of an occurrence (or disease).
300
The active form of vitamin-D (calcitriol) is produced by the enzyme 1-alpha-hydroxylase. What hormone activates this enzyme?
The precursor to calcitriol is stored in the skin where UV exposure converts it to previtamin D3. Then, it is bound to vitamin-D binding protein (DBP) where it is carried to the liver and metabolized to 25-hydroxyvitamin D. When Calcium is low, parathyroid hormone (PTH) levels become elevated which activates 1-alpha-hydroxylase which converts it to the active Vitamin D (calcitriol). Its most potent effect is to enhance intestinal calcium absorption through DNA regulation. Illustration A shows a diagram of Vitamin D metabolism.
300
Ligaments are viscoelastic, meaning that their tensile strength is affected by
1. Torsion and tension only 2. Orientation of applied strain 3. Rate of applied load 4. Compression only 5. Tension only Ligaments are viscoelastic material which means their stress-strain curve patterns are time/rate dependent (as a result of the internal friction). The inital portion of the stress-strain curve, called the toe region, exhibits a high deformation/low force characteristic due to the uncrimping of collagen fibers and the elasticity of elastin. Next is the linear region where slippage within and then between collagen fibrils occurs. In this stage, ligaments gets stiffer (increased tensile strength) at higher strain rates. Illustration A shows the different regions of the stress-strain curve.
300
Titanium and its alloys are unsuitable candidates for which of the following implant applications?
PREFERRED RESPONSE: 2 DISCUSSION: Titanium alloy is highly biocompatible, has higher strength than stainless steel, and is highly resistant to corrosion. It is particularly suited for use in fracture plates, bone screws, and intramedullary nails because of its low modulus of elasticity (low stiffness), which can reduce stress shielding. It is also widely used for porous-ingrowth coatings. However, clinical experience has shown that titanium alloy bearing surfaces such as a femoral ball are highly susceptible to severe metallic wear, particularly in the presence of third-body abrasive particles (PMMA fragments, bone chips, metal debris, etc).
300
An 85-year-old patient diagnosed with osteoporosis is begun on a bisphosphonate. What can you tell her about her risk of vertebral fracture after 3 years of treatment? Ie % increase/decrease??
The answer for this question specifically targets the work done by Harris et. al in the JAMA article. When patients were treated with bisphosphonates (risendronate, 5mg/day), the incidence of new vertebral fractures was reduced by 65% following one year of treatment and by 41% following 3 years of treatement. In addition to these findings, the authors noted a 39% decrease in incidence of non-vertebral fractures and a significant increase in bone mineral density.
300
While conducting a retrospective review of patients undergoing two different techniques for open reduction and internal fixation of ankle fractures, the investigator would like to assess whether there is any significant difference between the mean patient age in the two groups. The two groups are normally distributed. Which of test would be most appropriate?
PREFERRED RESPONSE ▼ 1 A Student-test would be the most appropriate test for analyzing means of parametric (continuous) variables that are normally distributed between two groups. Data can be characterized as non-parametric (categorical, ordinal) or parametric (continuous). Parametric data, such as age, are observations for which difference between the numbers have meaning on a numerical scale. Non-parametric data are observations which can be expressed as a dichotomous (yes or no) outcome such as gender. Kocher and Zurakowski present a Level 5 review of epidemiology and biostatistics. The authors state that univariate or bivariate analysis, such as the student t-test, is used to assess the relationship of a single independent and a single dependent variable. Incorrect Answers: Answer 2: Analysis of variance is used to evaluate means of parametric data between three or more groups when the data is normally distributed Answer 3: Fisher exact test is used to compare proportions for non-parametric data when the expected frequency is small (less than five per group) Answer 4: Kruskal-Wallis test is used to evaluate medians of three or more groups when the data are not normally distributed. Answer 5: Chi-square test is used to compare proportions for categorical or ordinal data (non-parametric)
400
List 3 radiograhic changes that can be seen in Rickets in children?
Widened physis Irregular Metaphysis Anterior rib widening (rachitic rosary) DISCUSSION: Rickets is a condition of inadequate mineralization of osteoid and cartilage at the growing ends of bone in children. It is associated with a nutritional deficiency in children that affects open physes, as opposed to osteomalacia which is a deficiency in people with closed growth plates. There are classic radiographic findings and disorders that mimic: rickets. Classic findings are widened physes related to widening of the physis fr om accumulation of nonmineralized osteoid and cartilage, irregular metaphyses, and loss of definition of the zone of provisional calcification. The changes are seen predominantly in the bones with greatest growth (tibia, distal fe mur, distal radius) and rarely seen in slower growing bones such as the tubular bones in the hand. Widening of the anterior ribs, the rachitic rosary, may be seen. Hyperparathyroidism with accumulation of fibrous tissue in the metaphyses can produce lucencies that may appear similar to the nonmineralized osteoid of rickets. Hyperparathyroidism has erosion around the edge of the growth plate. There are punched out lesions and resorption subperiosteally. Rounded epiphyses and marked separation of the epiphysis and metaphysis are the classic differentiation of Jansen syndrome, a dominantly inherited metaphyseal chondrodysplasia. Sclerotic metaphyseal ends are similar to rickets, but with maturation, the spaces fill with irregular calcification classic to Jansen syndrome. Sclerotic of the vertebra, or "rugger jerscy" spine, is typical of renal osteodystrophy.
400
A hip compression screw is placed in a test jig and a bending load is applied to the tip of the screw. After the load is released, the screw returns completely to its original shape. What is this type of deformation called?
l. Plastic 2. Elastic 3. Fatigue 4. Creep 5. Torsion PREFERRED RESPONSE: 2 DISCUSSION: When an implant is loaded below the yield point, by definition, it undergoes elastic deformation, meaning that all of the deformation recovers when the load is removed. If it is loaded above the yield point, then plastic or permanent deformation occurs. Fatigue is the gradual accumulation and progression of cracks in the material, which, after many cycles of loading, can lead to gross failure. Creep is the gradual accumulation of permanent (plastic) deformation over time, which may occur with polymeric materials but is not typical of metals or ceramics. Torsion refers to a torque being applied about the long axis of a bone or an implant. In general, the materials and dimensions of an implant are chosen to avoid plastic deformation or fa tigue fa ilure during typical clinical use.
400
Stiffness relates the amount of load applied to a structure like a long bone or an intramedullary nail to the amount of resulting deformation that occurs in the structure. What is the most important material property affecting the axial and bending stiffness of a structure
1- Elastic modulus 2- Ductility 3- Ultimate stress 4- Yield stress 5- Toughness PREFERRED RESPONSE: 1 DISCUSSION: 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).
400
Which of the following changes of calcium metabolism accompany the loss of bone during menopause? ________ changes in external calcium balance with a ________ in intestinal calcium absorption and an ________ in urinary calcium loss
Negative changes in external calcium balance with a decrease in intestinal calcium absorption and an increase in urinary calcium loss
400
A study was conducted in 500 patients to measure the effectiveness of a new growth factor in reducing healing time of distal radial fractures. The authors reported that average healing time was reduced from 9.2 to 8.9 weeks (P < 0.0001). Because the difference was highly statistically significant, they recommended routine clinical use of this drug despite its high cost. A more appropriate interpretation of these results is that they are
1- clinically significant. 2- statistically significant but perhaps not clinically significant. 3- statistically and clinically significant. 4- not statistically or clinically significant. 5- nonconclusive. PREFERRED RESPONSE: 2 DISCUSSION: 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.
500
What are PTH 3 actions on bone?
Stimulate osteoblasts Osteoblasts produce RANKL RANKL stimulates osteoclasts
500
The radiographs of a cemented total knee arthroplasty show substantial amounts of osteolysis underneath the tibial baseplate. There is no evidence of excessive wear of the superior surface of the polyethylene. The patient has had no previous implants, and the prosthesis has no intramedullary stem. What is the most probable cause of the osteolysis?
1. Stress shielding caused by the implant, leading to bone resorption 2. Polyethylene wear debris fr om the tibiofemoral surface articulation 3. Metal wear debris from the tibiofemoral surface articulation 4. Cement debris from the cement-bone fixation surfaces 5. Polyethylene fretting wear debris from the backside of the insert PREFERRED RESPONSE: 5 DISCUSSION: A number of studies have shown that in some designs of total knee implants, micromotion and fretting between the backside of the polyethylene insert and the tibial tray can generate significant amounts of wear debris, sufficient to cause substantial osteolysis. Stress shielding is not a likely cause in this case because there is no intramedullary stem. In general, articulation of metal against polyethylene generates insignificant amounts of metal wear debris.
500
A surgeon plans to stabilize a fracture in the distal third of a fe mur shaft using an intramedullary naiL Two types of nails are available that have identical dimensions (diameter, wall thickness, curvature, etc.), one made of stainless steel and the other of titanium alloy. The elastic modulus of stainless steel is about double that of titanium alloy. What is a potential advantage of the titanium alloy nail in this situation?
1. It has a higher fa tigue strength. 2. It can bend more easily, to accommodate the curvature of the femur. 3. During healing, the fracture will experience smaller interfragmentary motion with the titanium nail. 4. Titanium alloy is more resistant to fretting wear. 5. Corrosion is less likely with the titanium alloy naiL PREFERRED RESPONSE: 2 2010 Orthopaedic Basic Science Examination Answer Book · 37 DISCUSSION: Because its elastic modulus is 50% lower, the more flexible titanium alloy nail will require about 50% less bending fo rce to conform to the curvature of the canal. This means that it will require substantially less axial force (hammering) to drive the nail down the canal, reducing the likelihood of iatrogenic comminut ion. For an equal amowlt of weight bearing, the lower stiffness of the titanium alloy nail will result in larger interfragmentary motions at the fr acture. Stainless steel has a higher fat igue resistance than titanium alloy. As long as the metals are not mixed (for example, stainless steel screws used with a titanium alloy nail), corrosion should not be a problem with either alloy.
500
Randomized clinical trial showed that bisphosphonate treatment was _____ effective at preventing head collapse than placebo at 2 years (bisphosphonate collapse _____ %vs placebo collapse ____%)
randomized clinical trial showed that bisphosphonate treatment was more effective at preventing head collapse than placebo at 2 years (bisphosphonate collapse 6.9% vs placebo collapse 76%)
500
A research study is initiated on 500 patients undergoing total hip arthroplasty. The patients are fo llowed and outcome is assessed according to body mass index (BMI). The effects ofBMI on outcome should be reported as ?
1. Odds ratio 2.Incidence rates 3.Prevalence rates 4. Relative risk 5. Confidence intervals PREFERRED RESPONSE: 4 DISCUSSION: The study describes an example of a cohort study. Cohort studies fo llow a group of individuals over time and are optimal fo r studying the incidence, course, and risk fa ctors of a disease. The effects in a cohort study are frequently reported in terms of relative risk (RR). Odds ratios are used to report effects in a case-control study. Incidence and prevalence rates are descriptors of a given characteristic either developed over time (incidence) or at one given time (prevalence). Confidence intervals are used to convey the significance of findings and are often used in lieu of or in conjunction with P values.
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