10
Basic Science
Bone
Osteoblasts, Osteoclasts, and Osteocytes
Osteoblasts
| 1. | From which cells do osteoblasts arise? | 1. | Undifferentiated mesenchymal stem cells (MSCs) |
| 2. | What seven growth factors influence osteoblast differentiation? | 2. | Interleukins (ILs) Insulin-like growth factor (IGF-I) Platelet-derived growth factor (PDGF) Bone morphogenic proteins (BMPs) Transforming growth factor-β (TGF-β) Osterix Runx 2 (formerly Cbfa 1) |
| 3. | What is the function of IGF? | 3. | Osteosynthesis |
| 4. | Through what intracellular signaling pathway does it work? | 4. | Tyrosine kinase |
| 5. | What is the function of PDGF? | 5. | Chemotaxis |
| 6. | Through what intracellular signaling pathway does it work? | 6. | Tyrosine kinase |
| 7. | What is the function of BMP? | 7. | Stimulates mesenchymal cell differentiation |
| 8. | Through what intracellular signaling pathway does it work? | 8. | Serine/threonine kinase through SMAD proteins |
| 9. | Is BMP osteoinductive or osteoconductive? | 9. | Osteoinductive |
| 10. | TGF-b stimulates mesenchymal cells to produce what two substances? | 10. | Type II collagen Proteoglycans |
| 11. | TGF-b also indirectly stimulates osteoblasts to produce what? | 11. | Type I collagen |
| 12. | Through what intracellular signaling pathway does it work? | 12. | Serine/threonine kinase |
| 13. | What four substances do osteoblasts produce? | 13. | Alkaline phosphate Type I collagen Osteocalcin RANK ligand |
| 14. | Osteoblasts respond directly to what five factors? | 14. | Parathyroid hormone (PTH) Glucocorticoids Prostaglandins 1,25-vitamin D Estrogen |
| 15. | Which two of these favor osteogenesis? | 15. | 1,25-vitamin D Estrogen |
| 16. | Which three favor resorption? | 16. | PTH (resorption releases calcium) Glucocorticoids Prostaglandins |
| 17. | What two factors upregulate adenylate cyclase at the cellular level? | 17. | PTH Prostaglandins |
| 18. | What factor downregulates adenylate cyclase? | 18. | Estrogen |
| 19. | What factor also decreases calcium absorption at the level of the gut? | 19. | Glucocorticoids |
Osteoclasts
| 20. | From what cells do osteoclasts arise? | 20. | Monocyte progenitors |
| 21. | How do osteoclasts bind to the surface of bone? | 21. | With integrins (vibronectin) |
| 22. | Where does resorption occur? | 22. | Howship’s lacunae |
| 23. | What are the two products of osteoclasts? | 23. | Hydrogen ions (through carbonic anhydrase) Tartrate resistant acid phosphatase |
| 24. | What do osteoclasts respond directly to? | 24. | Calcitonin |
| 25. | What is the effect of calcitonin on the osteoclast? | 25. | Inhibits osteoclast function |
| 26. | What is the effect of IL-1? | 26. | Stimulates osteoclast function |
| 27. | What is the effect of IL-10? | 27. | Inhibits osteoclast function |
| 28. | What is the effect of IL-11? | 28. | Increases production of RANK ligand |
| 29. | What is the function of RANK ligand? | 29. | Links osteoblast and osteoclast function |
| 30. | What cell contains RANK ligand? | 30. | Osteoblast |
| 31. | How does RANK ligand work? | 31. | Binds to and stimulates osteoclasts |
| 32. | What cofactor is required? | 32. | Macrophage colony-stimulating factor (M-CSF) |
| 33. | What inhibits the RANK stimulation of osteoclasts? | 33. | Osteoprotegerin |
| 34. | How? | 34. | Blocks RANK binding to the osteoclast, competitive inhibition |
Hormonal Effects on Bone Metabolism
| 35. | If considering estrogen replacement therapy, when should it be started for maximal benefit? | 35. | Within 5 to 10 years of menopause |
| 36. | Generally speaking, how does estrogen work? | 36. | Decreases both bony resorption and formation But resorption is decreased much more than formation |
| 37. | What are two pharmacologic alternatives to estrogen therapy? | 37. | Alendronate Raloxifene |
Osteocytes
| 38. | What are osteocytes stimulated by? | 38. | Calcitonin |
| 39. | What are osteocytes inhibited by? | 39. | PTH |
| 40. | How does mechanical stimulation work? | 40. | Increases prostaglandin E2 production (stimulus) |
| 41. | How are osteons connected to one another? | 41. | By haversian canals |
| 42. | What are the extensive networks of osteonal processes that allow communication? | 42. | Canaliculi |
| 43. | What is the outer osteonal border called? | 43. | Cement line |
| 44. | What lies in between osteons? | 44. | Interstitial lamellae |
Composition of Bone
| 45. | What is the principal organic component of bone? | 45. | Type I collagen |
| 46. | What is the composition of a collagen fibril? | 46. | Two α1 chains Two α2 chains |
| 47. | How is collagen secreted? | 47. | Secreted as procollagen |
| 48. | Then what happens? | 48. | Cross-linked after secretion |
| 49. | What is the difference between a hole and a pore? | 49. | Holes are the spaces between the ends of collagen molecules Pores are the spaces between the sides of the collagen molecules |
| 50. | What are the three noncollagenous matrix proteins of bone? | 50. | Osteocalcin Osteonectin Osteopontin |
| 51. | What stimulates osteocalcin production? | 51. | 1,25-vitamin D |
| 52. | What inhibits osteocalcin production? | 52. | PTH |
| 53. | Osteocalcin attracts what cell type? | 53. | Osteoclasts |
| 54. | What are osteocalcin levels a marker of? | 54. | Bone metabolism |
| 55. | Bone mineralization consists of what two processes? What are the key features of each? | 55. | Initiation (sialoproteins, pores, high-energy requirement) Growth (osteocalcin, coalescing areas of mineralization) |
| 56. | What are the three laboratory markers of bone resorption? | 56. | Urinary hydroxyproline Urinary pyridoline N-telopeptide |
| 57. | What are the laboratory markers of bone formation? | 57. | Alkaline phosphate |
Properties of Mature Bone
| 58. | Normal mature bone is of what type? | 58. | Lamellar |
| 59. | What is the defining characteristic of lamellar bone? | 59. | Remodeled along lines of stress |
| 60. | What are the two subtypes of lamellar bone? | 60. | Cortical Cancellous |
| 61. | In contrast, immature or pathologic bone is of what type? | 61. | Woven |
| 62. | Bone is strongest in what direction? Weakest in what direction? | 62. | Strongest in compression Weakest in shear |
| 63. | When bone is under torsion, where is the greatest load experienced? | 63. | Maximum load experienced at 45 degrees to the long axis of the bone |
| 64. | What is the basic premise of Wolff’s law? | 64. | Increased stress leads to increased bone formation |
| 65. | Piezoelectric charges: is compression electropositive or negative? | 65. | Compression results in a negative charge |
| 66. | The negative charge then leads to what process? | 66. | Bone formation |
| 67. | Is tension electropositive or negative? | 67. | Positive charge |
| 68. | What does the positive charge lead to? | 68. | Bone resorption |
| 69. | What is the Heuter-Volkmann law? Give an example of where this law applies. | 69. | Compression inhibits growth Tension stimulates growth Example: scoliosis |
| 70. | At what age is peak bone mass achieved? | 70. | End of the third decade of life (the 20s) |
| 71. | What is the annual rate of bone loss after peak? | 71. | 0.3 to 0.5% per year |
| 72. | What is the annual rate of bone loss after menopause, without treatment? | 72. | 2 to 3% per year for 6 to 10 years after menopause |
| 73. | Is the observed postmenopausal decline simply estrogen related? | 73. | Not just estrogen, but changes in calcium metabolism also Decreased intestinal calcium absorption Increased calcium losses |
Blood Supply of Mature Bone
| 74. | Is the nutrient system high or low pressure? | 74. | High pressure |
| 75. | What does it supply? | 75. | Inner two thirds of bone |
| 76. | Is the periosteal system high or low pressure? | 76. | Low pressure |
| 77. | What does it supply? | 77. | Outer one third of bone |
| 78. | In what direction does blood flow in the adult? | 78. | Nutrient to periosteal |
| 79. | In what direction does blood flow in immature bone? | 79. | Opposite direction of flow |
Fracture Healing
| 80. | What is the principal determinant of fracture healing? | 80. | Blood supply |
| 81. | What are the three components of the sequence of changes in blood supply after fracture? | 81. | Immediate decrease in blood supply Increased vascularity (maximal at 2 weeks) Return to normal by 3 to 5 months |
| 82. | What is the effect of reaming? | 82. | Destroys endosteal blood supply |
| 83. | What are the three effects of nicotine on fracture healing? | 83. | Increased time to fracture healing Increased risk of nonunion Decreased fracture callus strength |
| 84. | Nicotine use is associated with increased risk of fractures at which locations? | 84. | Increases risk of wrist and hip fractures |
| 85. | How does smoking affect lumbar fusion rates? | 85. | Increases the pseudarthrosis rate of lumbar fusion by 500% |
| 86. | What is the two-step sequence of callus types formed after fracture? | 86. | Bridging (soft) callus within 2 weeks Replaced by woven bone (hard callus) |
| 87. | Callus is ultimately remodeled over what period? | 87. | Remodeled to lamellar bone within 7 years |
| 88. | What two types of bone formation are seen with cast treatment of fracture? | 88. | Periosteal bridging callus Enchondral ossification |
| 89. | Is there any difference with intramedullary (IM) nail treatment? | 89. | IM nail treatment also results in medullary callus formation late |
| 90. | Under what two conditions can intramembranous bone formation (no cartilage precursor) be seen after fracture? | 90. | Low strain High oxygen tension |
| 91. | What type of chondrocytes are present in the first 10 days after fracture? | 91. | Proliferative chondrocytes |
| 92. | What collagen type do they produce? | 92. | Type II |
| 93. | What other collagen type is present in the chondroid phase? | 93. | Type IX: cross-linking function |
| 94. | After 14 days, what chondrocyte type is present? | 94. | Hypertrophic chondrocytes |
| 95. | What type of collagen do they produce? | 95. | Type X |
| 96. | What are the next three steps? | 96. | Calcification Osteoclasts resorb matrix Osteoblasts lay down new bone |
| 97. | How do hypertrophic nonunions heal? | 97. | Mineralization of fibrocartilage |
| 98. | What other treatment modality has a similar mechanism? | 98. | Pulsed electromagnetic field treatment (bone stimulator) |
| 99. | Rate the four tissue types from highest to lowest strain tolerances? | 99. | Granulation tissue (100% strain tolerance) Fibrous tissue Cartilage Bone |
Additional Fracture Treatment Modalities
| 100. | At what phase of fracture healing does direct current exert an effect? | 100. | Inflammatory-response phase |
| 101. | At what phase of fracture healing does alternating current exert an effect? | 101. | Repair phase (callus) |
| 102. | What is the effect of pulsed electromagnetic fields? | 102. | Initiates fibrocartilage calcification |
| 103. | What is the classic application of this technology? | 103. | Nonhealing pseudo-Jones fracture |
| 104. | What are the two benefits of pulsed low-intensity ultrasound? | 104. | Accelerated fracture healing Increased callus strength |
| 105. | What are the two detrimental effects of radiation? | 105. | Decreased cellularity Decreased callus strength |
Distraction Osteogenesis
| 106. | How long should the latency phase last? | 106. | 5 to 7 days |
| 107. | What is the desired rate of distraction during distraction phase? | 107. | 1 mm/day |
| 108. | What is the duration of the consolidation phase? | 108. | Twice as long as the distraction phase |
| 109. | What is the weight-bearing status throughout treatment? | 109. | Weight-bearing as tolerated (WBAT) |
| 110. | What changes are seen in blood vessels? | 110. | Proliferation of vasa vasorum |
| 111. | What is the oxygen tension with distraction osteogenesis? | 111. | High oxygen tension |
| 112. | So what type of bone formation is seen under these low-strain, high oxygen tension conditions? | 112. | Intramembranous bone formation (no cartilage precursor) |
Calcium and Phosphate Metabolism: Key Concepts
Calcium
| 113. | What is the daily calcium intake recommendation for healthy children and adults? | 113. | 750 mg |
| 114. | What is the daily calcium intake recommendation for teenagers, pregnant women, and individuals with healing fractures? | 114. | 1500 mg |
| 115. | What is the daily calcium intake recommendation for lactating mothers? | 115. | 2000 mg |
| 116. | What is the mechanism of calcium absorption in the duodenum? | 116. | Active transport |
| 117. | What is the mechanism of calcium absorption in the jejunum? | 117. | Passive diffusion |
| 118. | What is the mechanism of calcium absorption in the kidney? | 118. | Proximal tubular resorption |
| 119. | What percentage of total body calcium is within plasma? | 119. | 1% |
| 120. | What are the relative proportions of bound vs. unbound plasma calcium? | 120. | Bound = unbound |
| 121. | What are the two principal regulators of plasma calcium concentration? | 121. | PTH 1,25-vitamin D |
Phosphate
| 122. | What are the relative proportions of bound vs. unbound plasma phosphate? | 122. | Unbound predominates |
| 123. | What is the principal site of phosphate resorption within the kidney? | 123. | Proximal tubule |
Parathyroid Hormone
| 124. | What type of molecule is parathyroid hormone (PTH)? | 124. | Peptide |
| 125. | Where is PTH produced? | 125. | Chief cells of the parathyroid gland |
| 126. | What is the stimulus for release of PTH? | 126. | Low plasma calcium concentration |
| 127. | What receptor detects calcium concentration? | 127. | Calcium sensing receptor (CaSR) |
| 128. | In what organ and gland can this receptor be found? | 128. | Kidney Parathyroid gland |
| 129. | What type of receptor is CaSR? | 129. | G-protein-coupled receptor |
| 130. | What are the three effects of CaSR activation within the parathyroid gland? | 130. | PTH secretion PTH gene expression Cellular proliferation |
| 131. | In what organ and in what cells can PTH receptors be found? | 131. | Kidney Osteoblasts |
| 132. | What are PTH’s two actions on the kidney? | 132. | Increase 1,25-vitamin D production Decrease resorption of renal phosphate |
| 133. | What are PTH’s three actions on the bone? | 133. | Stimulate osteoblasts Osteoblasts produce RANK ligand RANK ligand stimulates osteoclasts |
| 134. | What is the net effect of PTH on plasma calcium and phosphate concentrations? | 134. | Increased plasma calcium Decreased plasma phosphate |
1,25-Vitamin D
| 135. | What type of molecule is 1,25-vitamin D? | 135. | Steroid |
| 136. | As vitamin D is activated to 1,25-vitamin D, what are the two sites of hydroxylation? | 136. | First: liver Second: kidney |
| 137. | What are the three stimuli for release of 1,25-vitamin D? | 137. | Low serum calcium concentration Low serum phosphate concentration Elevated PTH levels |
| 138. | What are the two effects of 1,25-vitamin D? | 138. | Increased intestinal absorption of calcium and phosphate Increased osteoclast activity |
| 139. | What is the net effect of 1,25-vitamin D on plasma calcium and phosphate concentrations? | 139. | Increased plasma calcium Increased plasma phosphate |
Calcitonin
| 140. | What type of molecule is calcitonin? | 140. | Peptide |
| 141. | Where is calcitonin produced? | 141. | Clear cells (parafollicular cells) of the thyroid gland |
| 142. | What is the stimulus for release of calcitonin? | 142. | Elevated serum calcium |
| 143. | What is the effect of calcitonin? | 143. | Inhibits osteoclast activity |
Calcium and Phosphate Metabolism: Pathologic States
Primary Hyperparathyroidism
| 144. | What is a common cause of primary hyperparathyroidism? | 144. | Adenoma of one parathyroid gland |
| 145. | If four glands are affected, what diagnosis must be considered? | 145. | Multiple endocrine neoplasia (MEN) syndrome |
| 146. | What is the effect of primary hyperparathyroidism on 1,25-vitamin D levels? | 146. | Increased 1,25-vitamin D |
| 147. | What is the effect of primary hyperparathyroidism on serum calcium concentration? | 147. | Increased serum calcium |
| 148. | What is the effect of primary hyperparathyroidism on serum phosphate concentration? | 148. | Decreased serum phosphate |
| 149. | What is the hydration status of hypercalcemic patients? | 149. | Generally dehydrated as hypercalcemia leads to polyuria |
| 150. | What is osteitis fibrosa cystica? | 150. | Resorption of bone due to PTH overactivity and replacement with fibrous tissue |
| 151. | What are the two characteristic histologic features of brown tumors? | 151. | Giant cells Hemosiderin |
| 152. | What are the other systemic effects of hypercalcemia? | 152. | Renal stones Psychiatric disorders Abdominal pain |
| 153. | What are the four available hypercalcemia treatment methods? | 153. | Saline hydration Loop diuretics Dialysis Mobilization |
Hypoparathyroidism
| 154. | What is the most common cause of hypoparathyroidism? | 154. | Iatrogenic |
| 155. | What is the effect on serum calcium concentration? | 155. | Decreased serum calcium |
| 156. | What is the effect on serum phosphate concentration? | 156. | Increased serum phosphate (because low PTH levels) |
| 157. | What is the effect on 1,25-vitamin D levels? | 157. | Decreased 1,25-vitamin D |
| 158. | What is the characteristic radiographic finding on skull films? | 158. | Calcification of the basal ganglia |
Pseudohypoparathyroidism
| 159. | What is the cause of pseudohypoparathyroidism? | 159. | No PTH effect at target cells |
| 160. | Inheritance? | 160. | X-linked dominant (XLD) |
| 161. | Quick review: what other disorder has a similar inheritance pattern? | 161. | Hypophosphatemic rickets |
| 162. | What gene is involved? | 162. | GNAS1 |
| 163. | Mutation? | 163. | Gα subunit |
| 164. | Quick review: in what two other clinical situations do G-proteins play a vital role? | 164. | Fibrous dysplasia CaSR function |
| 165. | What is the PTH level in pseudohypoparathyroidism? | 165. | Normal or high |
| 166. | What is the serum calcium concentration? | 166. | Low serum calcium |
| 167. | What is the serum phosphate concentration? | 167. | Elevated serum phosphate (again, no PTH effect) |
| 168. | What is the effect on 1,25-vitamin D levels? | 168. | Low 1,25-vitamin D |
| 169. | Give an example of a disorder associated with pseudohypoparathyroidism? | 169. | Albright syndrome |
| 170. | What are the four characteristic features of pseudohypoparathyroidism? | 170. | Short metacarpals Bony exostoses Obesity Mental retardation |
| 171. | Quick review: what is another disorder that is associated with obesity and mental retardation? | 171. | Prader-Willi |
Pseudopseudohypoparathyroidism
| 172. | Pseudopseudohypoparathyroidism is phenotypically similar to what? | 172. | Pseudohypoparathyroidism |
| 173. | What is the serum calcium concentration? | 173. | Normal |
| 174. | What is the target cell response to PTH? | 174. | Normal |
Renal Failure Osteodystrophy
| 175. | What are the two general types of renal failure osteodystrophy? | 175. | High turnover Low turnover (excess aluminum leads to decreased metabolic activity) |
| 176. | With the high turnover type, what is the serum phosphate level? | 176. | Elevated due to renal failure/inability to dump phosphate |
| 177. | … the serum calcium level? | 177. | Low because with elevated phosphate, calcium precipitates out of solution |
| 178. | … the PTH level? | 178. | Elevated, because high phosphate levels lead to secondary hyperparathyroidism |
| 179. | What are the two components of the treatment for high turnover renal osteodystrophy? | 179. | Phosphate binders (antacids) Activated oral vitamin D |
| 180. | With the low turnover type, what is the serum calcium level? | 180. | Normal |
| 181. | … the serum phosphate level? | 181. | Normal |
| 182. | … the PTH level? | 182. | Low |
| 183. | … the 1,25-vitamin D level? | 183. | Low because of impaired renal hydroxylase |
| 184. | With renal osteodystrophy, what is the clinical appearance of the spine? | 184. | Rugger jersey spine |
| 185. | What other disorder also exhibits a rugger jersey spine? | 185. | Osteopetrosis |
| 186. | What other generalized bony changes are present? | 186. | Osteitis fibrosa cystica due to secondary hypoparathyroidism |
| 187. | Chronic dialysis treatment also leads to what disorder? | 187. | Amyloidosis |
Renal Tubular Acidosis
| 188. | With renal tubular acidosis, what two ions are lost in the urine? | 188. | Sodium Calcium |
| 189. | What is the key lab value for diagnosis? | 189. | Urine calcium > serum calcium |
| 190. | What is the treatment of renal tubular acidosis? | 190. | Alkalinize the urine |
| 191. | Renal tubular acidosis is phenotypically similar to what disorder? | 191. | Rickets |
| 192. | Quick review: What are three other situations in which calcium losses can exceed intake? | 192. | Postmenopausal woman (increased urine calcium, decreased absorption) Elevated glucocorticoids (increased urine calcium) Osteogenic rickets (fibroblast growth factor-23 [FGF-23]) |
Rickets
Nutritional Rickets: Vitamin D Deficiency
| 193. | What is the suggested daily intake of vitamin D for healthy adults? | 193. | 200 international units (IU) |
| 194. | What is the suggested daily intake of vitamin D for children, pregnant women, and lactating mothers? | 194. | 400 IU |
| 195. | What is the only natural dietary source of vitamin D? | 195. | Oily fish |
| 196. | What is the serum calcium level with vitamin D deficiency? | 196. | Decreased (due to decreased absorption) |
| 197. | What is the resulting effect on PTH? | 197 | Increased (in response to low calcium) |
| 198. | What two clinical features of nutritional rickets are most sensitive and specific? | 198. | Wrist enlargement Costochondral enlargement |
| 199. | What is the serum phosphate level? | 199. | Decreased (due to high PTH) |
| 200. | What does treatment of vitamin D deficiency rickets consist of? | 200. | 5000 IU per day of vitamin D |
Nutritional Rickets: Calcium Deficiency
| 201. | Deficient calcium intake has what effect on PTH levels? | 201. | PTH levels become elevated |
| 202. | What effect does this have on vitamin D levels? | 202. | Increases vitamin D levels (attempt to absorb greater amounts of calcium, phosphate) |
| 203. | What are serum phosphate levels? | 203. | May actually be low (due to elevated PTH) |
| 204. | What is the treatment of calcium deficiency rickets? | 204. | 750 mg/day of calcium |
Nutritional Rickets: Phosphate Deficiency
| 205. | Deficient phosphate intake has what effect on PTH levels? | 205. | None (PTH responds only to high phosphate) |
| 206. | What effect does low serum phosphate have on vitamin D levels? | 206. | Increases vitamin D levels (attempt to absorb greater amounts of phosphate) |
| 207. | What is the treatment of phosphate deficiency rickets? | 207. | Oral phosphate supplementation |
Vitamin D-Dependent Rickets Type I
| 208. | Inheritance? | 208. | Autosomal recessive (AR) |
| 209. | Mutation? | 209. | Defect in renal 1,25-hydroxylase |
| 210. | What is the effect of defective hydroxylase? | 210. | No conversion of inactive vitamin D to active form |
| 211. | What is the characteristic clinical feature? | 211. | Rachitic rosary responsive to vitamin D |
| 212. | What is the resulting serum calcium level? | 212. | Decreased |
| 213. | What is the resulting serum phosphate level? | 213. | Decreased (due to decreased absorption) |
| 214. | What is the resulting serum PTH level? | 214. | Elevated (in response to low calcium) |
| 215. | What is the treatment of vitamin D-dependent rickets (VDDR) type I? | 215. | Oral activated vitamin D |
Vitamin D-Dependent Rickets Type II
| 216. | Defect? | 216. | No receptor for 1,25-vitamin D at target cells |
| 217. | What is the serum level of 1,25-vitamin D? | 217. | Very high |
| 218. | What is the serum level of active vitamin D in type I? | 218. | Very low in type I |
| 219. | What are the two characteristic clinical features? | 219. | Alopecia Rachitic rosary unresponsive to vitamin D therapy |
| 220. | What is the treatment of VDDR type II? | 220. | Vitamin D analogue |
| 221. | What is the relative severity of both types of vitamin D dependent rickets vs. nutritional rickets? | 221. | Vitamin D dependent rickets I and II are more severe |
Hypophosphatemic Rickets
| 222. | What is the relative frequency of hypophosphatemic rickets as a cause of rickets? | 222. | Most common cause in the United States |
| 223. | What is the inheritance? | 223. | XLD |
| 224. | What is the mutation? | 224. | Impaired renal tubular absorption of phosphate |
| 225. | What is the gene? | 225. | PHEX |
| 226. | This disorder is also known as what? | 226. | Vitamin D resistant rickets |
| 227. | What is the serum phosphate level? | 227. | Low, because a lot of phosphate is lost in the urine |
| 228. | What is the resulting PTH level? | 228. | Normal (no PTH response to low serum phosphate) |
| 229. | What is the serum calcium level? | 229. | Normal |
| 230. | What is the classic triad of clinical features? | 230. | Short child Lower limb deformities Low serum phosphate |
| 231. | What are the two components of treatment of hypophosphatemic rickets? | 231. | High-dose phosphate replacement High-dose vitamin D (to facilitate phosphate absorption) |
Hypophosphatasia
| 232. | What is the inheritance? | 232. | AR |
| 233. | What is the defect? | 233. | Enzymatic deficiency leads to low levels of alkaline phosphate |
| 234. | Clinical features are similar to what group of disorders? | 234. | Nutritional rickets |
| 235. | How is hypophosphatasia diagnosed? | 235. | Elevated urinary phosphoethanolamine |
| 236. | What is the treatment of hypophosphatasia? | 236. | No good options exist |
Review of Key Points of Confusion
| 237. | High-turnover renal osteodystrophy displays clinical features similar to what other disorder? | 237. | Primary hyperparathyroidism (for example, osteitis fibrosa cystica) |
| 238. | The renal osteodystrophy spine has what appearance? | 238. | Rugger jersey spine |
| 239. | This spine appearance is also associated with what other disorder? | 239. | Osteopetrosis |
| 240. | Hypophosphatasia displays clinical features similar to what other disorder? | 240. | Nutritional rickets |
| 241. | The spine has what appearance in hypophosphatasia? | 241. | Rachitic rosary (like rickets) |
Paget’s Disease
| 242. | What are three proposed viral etiologies for Paget’s disease? | 242. | Respiratory syncytial virus (RSV) Paramyxovirus Canine distemper virus |
| 243. | What is the typical clinical presentation of Paget’s? | 243. | Bone pain |
| 244. | Within a given bone, how does Paget’s progress? | 244. | Starts at one end and progresses to the other |
| 245. | What is the radiographic appearance of progression? | 245. | Leading “lytic flame” |
| 246. | Laboratory findings include increased levels of what four substances? | 246. | Alkaline phosphate |
| Urinary hydroxyproline | |||
| Osteocalcin | |||
| N-telopeptide | |||
| 247. | What are the three key histologic features? | 247. | Osteoclasts with viral inclusion bodies (paramyxovirus) |
| Cement lines | |||
| Relative osteoblastic or osteoclastic appearance depends on phase of disease | |||
| 248. | What is the treatment of Paget’s disease? | 248. | Bisphosphonates |
| 249. | What other clinical conditions occur secondary to Paget’s disease in the spine? | 249. | Spinal stenosis |
| 250. | What other clinical conditions occur secondary to Paget’s disease in the heart? | 250. | High output cardiac failure |
| 251. | What other clinical conditions occur secondary to Paget’s disease in the auditory system? | 251. | Deafness |
| 252. | What does the new onset of severe pain and swelling in a patient with known Paget’s suggest? | 252. | Malignant osteosarcoma |
| 253. | How often does this occur? | 253. | In 10% of patients |
Osteoporosis
Aging and Bone Metabolism
| 254. | What effect does aging have on stomach acidity? | 254. | Decreased acidity |
| 255. | What effect does the change in acidity have on calcium absorption? | 255. | Decreased calcium absorption |
| 256. | What effect does aging have on vitamin D requirements? | 256. | Increased vitamin D requirements with age |
Osteoporosis
| 257. | Is osteoporosis a quantitative or qualitative deficiency of bone? | 257. | Quantitative (not enough bone) Compare to rickets (qualitative; poor quality bone) |
| 258. | What are the common laboratory findings in patients with osteoporosis? | 258. | Generally normal |
| 259. | What is the definition of osteoporosis in terms of T-score? | 259. | T-score of -2.5 or less |
| 260. | What are the two indications for treatment of osteoporosis? | 260. | T score of -2.5 History of any osteoporotic fracture |
| 261. | Compare the definitions of T-score and Z-score? | 261. | T-score is the number of standard deviations away from mean peak bone mass (comparison to 25-year-old population) Z-score is the number of standard deviations away from mean bone mass in age-matched population (comparison to population of the same age as the patient) |
| 262. | What two imaging modalities are most commonly used to arrive at a T-score? | 262. | Dual-energy x-ray absorptiometry (DEXA) scan Quantitative computed tomography (CT) scan |
| 263. | How much bone must be lost before a change in plain x-ray appearance is evident? | 263. | 30% |
| 264. | Does a DEXA scan evaluate cancellous and cortical bone individually? | 264. | No, together |
| 265. | Does a quantitative CT scan evaluate cancellous and cortical bone individually? | 265. | Yes, can separate |
| 266. | What is the downside of quantitative CT? | 266. | Increased radiation |
| 267. | What test is the most accurate for determining bone density? | 267. | Quantitative CT |
| 268. | What test is the most reliable for predicting fracture risk? | 268. | DEXA scan |
| 269. | What are the two general types of osteoporosis? | 269. | Type I: postmenopausal Type II: age related (>75 years old) |
| 270. | With type I osteoporosis, what type of bone is principally affected? | 270. | Trabecular bone (cancellous) |
| 271. | Give two examples of typical type I fractures? | 271. | Vertebral body fractures Distal radius fractures |
| 272. | With type II osteoporosis, what type of bone is principally affected? | 272. | Trabecular and cortical bone |
| 273. | Give two examples of typical type II fractures? | 273. | Hip fracture Pelvic fracture |
| 274. | How do bisphosphonates affect osteoclast microstructure? | 274. | Disrupt microtubules within the ruffled border |
| 275. | How do they disrupt macrostructure? | 275. | Disrupt protein prenylation |
| 276. | What disadvantageous effect do high-dose bisphosphonates have? | 276. | Disrupt calcium deposition also, not just resorption |
Osteoporosis in the Spinal Cord Injured Patient
| 277. | Over what period of time does the peak bone loss occur? | 277. | First 16 months after injury |
| 278. | After that period of time, how much bone mass remains? | 278. | Two thirds of the preinjury bone mass |
| 279. | What anatomic region is most affected by bone loss? | 279. | Knee |
| 280. | What anatomic region is most spared by bone loss? |
