MCQs – Metabolic 2

Modern Study Review (AI-Generated)

High-Yield Summary

Metabolic bone diseases and related arthropathies are a staple of the Royal College exam, focusing heavily on biochemical markers, radiographic features, and genetic inheritance patterns. The critical clinical decision often hinges on distinguishing between causes of mineralization defects (e.g., vitamin D malabsorption vs. phosphate wasting) and recognizing systemic disorders presenting with joint calcifications (e.g., hemochromatosis vs. CPPD). While classic exam answers emphasize biochemical thresholds and inheritance patterns, modern practice increasingly incorporates genetic testing and advanced imaging for early diagnosis. Understanding PTH and calcitonin physiology remains fundamental for interpreting calcium-phosphate disorders.

High-Yield Decision Matrix

Active Recall Q&A

Vitamin D Malabsorption & Osteomalacia

Q: What bone pathology should be suspected in gastrectomy or bowel resection patients with vitamin D malabsorption?
A: Osteomalacia characterized by increased unmineralized osteoid and decreased mineral apposition rate on tetracycline labeling.
Related Pearl: Tetracycline labeling remains the gold standard for assessing bone formation rates in metabolic bone diseases, differentiating osteomalacia from other causes of bone pain.

Vitamin D Resistant Rickets

Q: What is the inheritance pattern and pathophysiology of vitamin D resistant rickets (familial hypophosphatemic rickets)?
A: It is a sex-linked dominant trait caused by renal phosphate wasting leading to hypophosphatemia.
Related Pearl: Type I vitamin D resistant rickets involves defective renal phosphate reabsorption despite normal vitamin D levels, distinguishing it from nutritional rickets.

Secondary Gout

Q: Which hematologic disorders are commonly associated with secondary gout?
A: Myeloproliferative and lymphoproliferative disorders such as multiple myeloma, leukemia, erythrocytosis, and hemolytic diseases like sickle cell anemia.
Related Pearl: Increased cell turnover in these diseases elevates uric acid production, precipitating gout; this is a common exam trap confusing primary and secondary gout etiologies.

CPPD Workup

Q: What blood tests should be ordered in newly diagnosed CPPD patients?
A: Calcium, magnesium, phosphorus, glucose, alkaline phosphatase, ferritin, iron and iron binding capacity, TSH, and uric acid.
Related Pearl: Screening for hemochromatosis and metabolic disorders is critical as they can mimic or cause CPPD; ferritin and iron studies are essential.

Ochronosis (Alkaptonuria)

Q: What is ochronosis and what are its characteristic clinical and radiographic features?
A: Ochronosis is an inherited deficiency of homogentisic acid oxidase causing pigment deposition in cartilage, skin, and sclerae, leading to degenerative arthropathy starting in the 4th decade with vacuum discs and chondrocalcinosis.
Related Pearl: Dark urine that turns black on standing is a key clinical clue; early spine involvement with vacuum discs is distinctive.

Hemochromatosis Diagnosis and Arthropathy

Q: What are the diagnostic criteria and arthropathy features of hemochromatosis?
A: Autosomal recessive iron overload with ferritin markedly elevated, serum iron saturation ?60%, liver biopsy showing hemosiderin; arthropathy involves chondrocalcinosis mainly in MCP 2 & 3, PIP, shoulders, knees, hips.
Related Pearl: The large, radiodense liver on imaging is a classic diagnostic tip-off; chondrocalcinosis in the hands should always raise suspicion for hemochromatosis.

PTH Physiology

Q: How does PTH regulate calcium and phosphate homeostasis?
A: PTH increases vitamin D activation in the kidney, stimulates osteoclasts for bone resorption, increases renal phosphate excretion, and enhances calcium absorption in the gut and reabsorption in the kidney.
Related Pearl: PTH acts on the kidney for vitamin D hydroxylation, not the liver, a common exam pitfall.

Calcitonin Effects

Q: What is the effect of calcitonin on osteocytes and serum calcium?
A: Calcitonin directly stimulates osteocytes to lay down bone, decreasing serum calcium levels.
Related Pearl: Osteocytes play an active role in calcium homeostasis, not just osteoclasts and osteoblasts.

Hypocalcemia Clinical Sign

Q: What clinical sign is caused by hypocalcemia?
A: Carpo-pedal spasm.
Related Pearl: This sign reflects neuromuscular irritability due to low serum calcium and is a classic exam finding.

Mankin’s Rule

Q: What is Mankin’s rule regarding calcium and tissue irritability?
A: Irritability of nerve, brain, and skeletal muscle is inversely proportional to calcium levels, whereas cardiac muscle irritability is directly proportional to calcium.
Related Pearl: Explains why hypocalcemia causes tetany but hypercalcemia predisposes to cardiac arrhythmias.

Hypercalcemia Symptoms

Q: What are common symptoms of hypercalcemia?
A: Polyuria, polydipsia, constipation, lethargy, disorientation, and hyporeflexia.
Related Pearl: Hypercalcemia impairs renal concentrating ability causing polyuria and compensatory polydipsia.

Renal Osteodystrophy Features

Q: What are the skeletal manifestations of renal osteodystrophy?
A: Looser’s lines fractures, periostitis, osteitis fibrosa with subperiosteal erosions, and extraskeletal calcification causing leg pain.
Related Pearl: Looser’s zones are pseudofractures typical of osteomalacia and renal osteodystrophy, often missed on initial radiographs.

Steroid-Induced Bone Loss

Q: How do steroids cause bone loss?
A: By suppressing osteoblast activity, inhibiting intestinal calcium absorption causing secondary hyperparathyroidism, and increasing renal calcium excretion.
Related Pearl: Steroid-induced osteoporosis results primarily from decreased bone formation rather than increased resorption, guiding treatment strategies.

Myositis Ossificans Progressiva Lab Finding

Q: What laboratory finding is characteristic of myositis ossificans progressiva?
A: Increased alkaline phosphatase.
Related Pearl: Elevated alkaline phosphatase reflects active heterotopic bone formation and can help differentiate from other soft tissue masses.

Classic Clinical Notes

• Gastrectomy/bowel resection patients can have vitamin D malabsorption and end up with osteomalacia – look for increased unmineralized osteoid, with decreased rates of mineral apposition on tetracycline labeling.

• Vitamin D resistant rickets is also known as familial hypophosphatemic rickets and is inherited as a sex-linked dominant trait; it is caused by a renal inability to handle phosphate (there are a number of types of vitamin D resistant rickets, of which this is type I).

• Secondary gout is associated with myeloproliferative and lymphoproliferative disorders such as multiple myeloma, leukemia, erythrocytosis, and hemolytic diseases such as sickle cell.

• For newly diagnosed CPPD, you should get the following bloodwork: calcium, magnesium, phosphorus, glucose, alk phos, ferritin, iron and iron binding capacity, TSH, and uric acid. Patients with hemochromatosis often get a CPPD picture, and you should rule this out. Ochronosis is also associated with CPPD.

• Ochronisis (Alkaptonuria) – rare, inherited deficiency of homogentisic acid oxidase; homogentisic acid is retained in the body and deposited as a pigmented polymer in the cartilage, skin, and sclerae (the darkening of these tissues is called ochronosis). Because the pigment is preferentially deposited in cartilage, a degenerative arthropathy is inevitable, beginning in the 4th decade. It begins in the spine with multiple vacuum discs, then the entire spine showing ossification of discs and or narrowing and collapse. Look for chondrocalcinosis in multiple joints. Look for a history of passing dark urine, or fresh urine turning black on standing.

• Hemochromatosis – autosomal recessive disorder causing excessive body iron stores and deposition of hemosiderin causing tissue damage and organ dysfunction. Markedly elevated ferritin; increased serum iron concentration with at least 60% saturation of serum iron-binding transferrin. Diagnosis is confirmed by liver biopsy (the liver is radiodense too) showing hemosiderin in parenchymal cells; also may show fibrosis, cirrhosis, or even hepatoma. Chondrocalcinosis is characteristic of the arthropathy and a radiographic feature at some time in 50% of patients. The finding of chondrocalcinosis should always suggest the possibility of hemochromatosis. The arthropathy usually is of the hands, especially MCP (2 and 3) and PIP joints. May also get shoulders, knees, hips.

• The large, radiodense liver is the MCQ tip-off to think of hemochromatosis!

• PTH influences calcium hemostasis by influencing vitamin D production (amongst other things). Also gets osteoclasts working, and increases renal excretion of phosphate. Via vitamin D, it increases calcium absorption in the gut, increases calcium reabsorption in the kidney, and increases calcium breakdown from bone.

• Vitamin D (1,25 (OH)2 Vit D) is the most important for gut absorption of calcium.

• PTH does not work on the hydroxylation of vitamin D in the liver; it works at the kidney!

• Osteocytes are directly stimulated by calcitonin and inhibited by PTH; ? decrease serum calcium with calcitonin is due to osteocytes working to lay down bone?

• Carpo-pedal spasm is caused by hypocalcemia.

• Remember Mankin’s rules: nerve, brain, skeletal muscle – irritability is inversely proportional to calcium; while cardiac muscle irritability is directly proportional to calcium.

• Hypercalcemia – polyuria (phosphate diuresis), polydipsia, constipation, lethargy, disorientation, hyporeflexia.

• Renal osteodystrophy patients may have leg pain from extraskeletal calcification, fractures through Looser’s lines, periostitis, and osteitis fibrosa (subperiosteal erosions).

• Steroids produce bone loss primarily by suppressing osteoblasts. It inhibits intestinal calcium absorption, leading to mild secondary hyperPTH and osteoclastic absorption. It also stimulates renal calcium excretion.

• Myositis ossificans progressiva – has increased alk phos

Last Updated on January 25, 2026 by Christian Veillette