Paget's Disease- Epidemiology:
- Rare before 55
- Predominently European descent; Rare in AA and Asians and Indian Subcontinent
- Symptoms:
- Bone Pain (often worse with weight bearing) - thought to be due to increased metabolic activity
DDx of Pain in patients with Paget's Disease are Bone Pain (due to metabolic activity) - During rest and night
- Worse on weight bearing (making differentiation from OA challenging)
Nerve Compression Syndromes Pseudofractures ( narrow radiolucent bands
that traverse the cortex of long bones) Secondary OA Other musculoskeletal conditions
- Deafness
- Symptoms of complications
- i.e Pathological fractures, Nerve Compression, Secondary OA
- Signs: Warmth over the bone, bony deformity
- Diagnosis:
- Normal ALP does not rule out the disease
- Test for specific markers of bone turnover: ALP, Type I NTP (Useful if co-existence of liver disease)
- Radiographs, Radionuclide Bone Scan,
- Complications : Osteoarthritis, Spinal Stenosis, Pseudofractures, Osteosarcoma (< 0.5%), Obstuctive Hydrocephalus, High-output cardiac failure, Hypercalcemia of immobilization
- Treatment
- Indications:
- Bone Pain (no benefit in symptomatic patients)
- If OA is a differential and it is difficult to differentiate, therapeutic challenge can be done
Treated with bisphosphonates
- Psedofractures
- Asymptomatic: Observation
- Symptomatic i.e Pain
- Do NOT respond to Calcitonin
- Can progress to pathological fracture on bisphosphonates
- Surgical Stabilization is indicated if increasing pain in the affected site
- Treatment Options
- Bisphosphonates
- MOA: Bisphosphonates are synthetic analogues of inorganic pyrophosphate that are not biodegradable,
have skeletal half-lives measured in years, and
adhere to mineralized surfaces. They are ingested selectively by osteoclasts and disrupt energy
metabolism or specific enzymatic pathways.
- Amino-bisphosphonates or Nitrogen Containing Bisphosphonates (FIRST LINE)
- Better than simple bisphosphonate in decreasing ALP, but improving symptoms
- Alendronate (40 mg / day for 6 months)
- Osteonecrosis of Jaw has been reported with oral supplements
- Pamidronate
- Risedronate
- Zoledronic Acid
- Side effects of IV
- Acute phase response within 1-3 days; resolves completely in 7 days even without treatment; responds to acetaminophen
- Correct Vitamin D deficiency before treatment, and supplement calcium and Vitamin D for 1-2 weeks after infusion to avoid Hypocalcemia
- Simple bisphosphonates are
- Calcitonin
- 2nd line if bisphosphonates are CI
- MOA: Decreases bony turnover and decreases pain
- Denosumab (not licensed, may be useful)
- References
Joint Pain / Bony Pain case examples :Migrating Polyarthralgia- 1. 84 y/o Male Patient HTN, Aortic Stenosis, Heart block s/p Pacemaker placement, Anemia due to B12 deficiency is being seen for progressive increase in ALP (from 200 to >550) over a course of a year. GGT was slightly increased a year back. LFT were previously increased but is now normal. PT / INR is normal, and Bi is normal as well. He also has vertebral compression fracture of L1 and L2. Also, has pain in the shoulder region, and in hip. X ray confirms Pagets disease. How should you manage the patienr
- a. Zoledronic acid 5 mg IV infusion
- b. Alendronate 75 mg PO weekly
- c. Alendronate 40 mg PO daily
- d. Etidronate PO daily
- e. Clinical observation and symptomatic Treatment
- Answer cues:
- Symptomatic patients should be treated
- ALP normalizes in most patient in about a year
- Amino-bisphosphnates are preferred over simple bisphosphonates
- PO preferred over IV without contraindication
- Daily dose is given as against weekly dose
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