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OR7.1 | Metabolic Bone Disorders — PBL Case

CLINICAL SETTING

Mr. Krishnamurthy, a 74-year-old retired farmer from a rural district, presents to the orthopaedic outpatient clinic with a 3-year history of worsening pain in his right leg, progressive bowing of the right tibia noticed over 18 months, and difficulty hearing in both ears for the past year. His wife reports his skull appears 'larger than it used to be' and his hat size has increased. He has no history of trauma, malignancy, or metabolic illness. He has not sought medical care for over 10 years. On examination: his right tibia is visibly bowed anterolaterally, warm to touch with dilated superficial veins overlying it. The skull circumference is enlarged (62 cm). There is bilateral sensorineural hearing loss on tuning fork testing. No lymphadenopathy or organomegaly. Neurovascular examination of the lower limb is intact.

Trigger 1: Initial Assessment and Investigations

Plain X-rays are obtained. The right tibia shows cortical thickening, coarsened trabecular pattern, bowing, and alternating lytic-sclerotic areas. Skull X-ray shows marked thickening of the calvarium with a 'cotton-wool' appearance. Blood results: Serum calcium 2.38 mmol/L (normal), phosphate 1.12 mmol/L (normal), ALP 1,240 IU/L (markedly elevated; reference 30-120 IU/L), serum albumin normal, liver function tests otherwise normal, serum urate normal.

DISCUSSION POINTS

  • What is the most likely diagnosis based on the clinical and radiological findings? What is the pathophysiology of the bone changes seen in this condition?
  • Why is the ALP markedly elevated but calcium and phosphate are normal? What does this biochemical pattern tell you about the mechanism of bone turnover in this disease?
  • What other investigations would you order to stage the extent of disease and assess for complications? Justify each investigation.
Click to reveal Trigger 2: Disease Extent, Complications, and a New Concern (discuss previous trigger first!)

Trigger 2: Disease Extent, Complications, and a New Concern

A technetium-99m bone scan shows intense focal uptake in the right tibia, skull, lumbar spine (L3-L4), and right humerus. Audiometry confirms bilateral sensorineural hearing loss. Serum testosterone and PSA are normal. Three weeks after the initial visit, Mr. Krishnamurthy returns with sudden, severe right leg pain disproportionate to his previous baseline. X-ray now shows a new lytic lesion in the mid-tibia with cortical destruction and a soft tissue shadow. Repeat ALP is 8,400 IU/L — a tenfold increase from the baseline.

DISCUSSION POINTS

  • What is the most feared complication to consider given the new radiological finding and dramatic ALP rise? What is the incidence of this complication in this disease and what is its prognosis?
  • Explain the mechanism of deafness in this patient. Which cranial nerve is involved and how does the bone disease cause it?
  • What urgent investigations and multidisciplinary team involvement would you arrange for this patient now?
Click to reveal Trigger 3: Medical Management and Patient Counselling (discuss previous trigger first!)

Trigger 3: Medical Management and Patient Counselling

MRI confirms aggressive cortical destruction of the right tibia with a soft tissue mass extending beyond the bone; biopsy demonstrates osteosarcoma arising in pagetic bone. Meanwhile, the orthopaedic team reviews the uncomplicated pagetic sites (skull, spine, humerus). For these sites, the team plans to initiate bisphosphonate therapy to reduce bone turnover. The patient and his family ask: 'Can this medicine cure the disease? How long does he need to take it? Are there side effects?'

DISCUSSION POINTS

  • Which bisphosphonate is preferred for Paget's disease — oral alendronate or intravenous zoledronic acid? What is the dosing rationale, expected biochemical response, and duration of remission?
  • How would you counsel Mr. Krishnamurthy and his family about the natural history of Paget's disease, the goals of bisphosphonate therapy, and the monitoring required?
  • Reflecting on the full case: how does osteoporosis differ from osteomalacia and Paget's disease in terms of (a) biochemical profile and (b) radiological findings? Construct a comparison table covering Ca, PO4, ALP, vitamin D, and PTH for all three conditions.

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [OR7.1] What is the aetiopathogenesis of Paget's disease of bone? How does disordered osteoclast activity lead to the characteristic mixed lytic-sclerotic bone lesions?
  2. [OR7.1] What are the biochemical differences between osteoporosis, osteomalacia, and Paget's disease with respect to serum calcium, phosphate, ALP, vitamin D, and PTH? Under what circumstances can hypercalcaemia occur in Paget's disease?
  3. [OR7.1] What is the treatment protocol for Paget's disease with intravenous zoledronic acid? How is treatment response monitored and when is re-treatment indicated?
  4. [OR7.1] What are the recognised complications of Paget's disease? How does sarcomatous transformation present and what is the clue in the ALP trend?
  5. [OR7.1] How does deafness develop in Paget's disease? Which type of hearing loss predominates and why?
  6. [OR7.1] What are the clinical features, radiological signs (including Looser's zones), and management of osteomalacia? How does it differ biochemically from osteoporosis?
  7. [OR7.1] What are the deformities of nutritional rickets and how are they managed? What is the role of surgery versus medical treatment and at what age/stage is surgical correction considered?