Endocrinology

Osteoporosis and Bone Metabolism

Clinical overview and exam mastery guide covering antiresorptive and anabolic therapies, dosing regimens, administration rules, and fracture-risk strategy.

Diagnostic Anchor
T-score -2.5 or lower
First-Line Class
Bisphosphonates
Denosumab Schedule
Every 6 months
Teriparatide Limit
2 years lifetime

Bone Therapy Classes at a Glance

Antiresorptive bisphosphonate denosumab, SERM Anabolic teriparatide romosozumab Foundation calcium vitamin D Regimen choice is fracture-risk and tolerance based Oral adherence, renal function, and prior fractures guide escalation

Use antiresorptive or anabolic strategy based on risk severity and contraindications.

1. Definition

Osteoporosis is decreased bone mass with microarchitectural deterioration, causing increased fracture risk. Diagnostic anchors include T-score -2.5 or lower or a fragility fracture.

2. Risk Factors

Postmenopausal state Chronic glucocorticoids Smoking and alcohol Low BMI CKD Hypogonadism

3. Treatment Overview

First-Line for Most

  • Bisphosphonates

Other Options

  • Denosumab
  • Teriparatide
  • Romosozumab
  • SERMs or hormone therapy in selected patients

4. Calcium and Vitamin D

Supplement Dose Regimen MOA / Role Side Effects
Calcium 1000-1200 mg elemental calcium daily, split if over 500 mg per dose Provides mineral substrate for bone maintenance Constipation, kidney stone risk at excessive dosing
Vitamin D (cholecalciferol) 800-1000 IU daily; deficiency repletion 50,000 IU weekly for 6-8 weeks Increases calcium absorption and supports mineralization Hypercalcemia with excessive intake

5. Bisphosphonates (First-Line)

MOA for class: bind bone surface and inhibit osteoclast-mediated bone resorption.

Agent Dose Regimen Key Administration / Use Side Effects Contraindications
Alendronate 70 mg orally weekly or 10 mg daily Morning empty stomach, full glass water, remain upright 30 minutes Esophagitis, rare jaw osteonecrosis, atypical femur fracture with prolonged use Esophageal motility disorders, inability to sit upright, hypocalcemia
Zoledronic acid 5 mg IV once yearly Useful when oral therapy is not tolerated Acute phase flu-like reaction, hypocalcemia Severe renal impairment, hypocalcemia

6. Denosumab

  • MOA: monoclonal antibody against RANKL, suppressing osteoclast activation
  • Dose regimen: 60 mg subcutaneous every 6 months
  • Side effects: hypocalcemia, skin infections, rare jaw osteonecrosis
  • Contraindication: hypocalcemia
  • High-yield caution: abrupt discontinuation can trigger rebound vertebral fractures

7. Teriparatide

  • MOA: recombinant PTH analog with intermittent anabolic stimulation of bone formation
  • Dose regimen: 20 mcg subcutaneous daily
  • Maximum duration: 2 years lifetime
  • Side effects: hypercalcemia, dizziness
  • Contraindications: bone malignancy risk states, Paget disease
  • Use context: severe osteoporosis or multiple fragility fractures

8. Romosozumab

  • MOA: sclerostin inhibition increases bone formation and decreases resorption
  • Dose regimen: 210 mg subcutaneous monthly
  • Maximum duration: 12 months
  • Side effect concern: possible increased cardiovascular event risk
  • Contraindication: recent myocardial infarction or stroke

9. SERMs (Raloxifene)

  • MOA: selective estrogen receptor modulation reduces bone resorption
  • Dose regimen: 60 mg orally daily
  • Side effects: hot flashes, venous thromboembolism risk
  • Contraindication: prior thromboembolic disease

10. Glucocorticoid-Induced Osteoporosis

Consider treatment when prednisone-equivalent dose is 5 mg/day or more for at least 3 months. Preferred initial therapy is often a bisphosphonate.

Management Recap Drill

All patients: ensure calcium and vitamin D adequacy.
First-line: weekly oral alendronate when tolerated.
Oral intolerance: consider yearly zoledronic acid or denosumab every 6 months.
Very high fracture risk: use anabolic strategy such as teriparatide.

Visual Algorithm Placeholder

[Insert Osteoporosis Treatment Algorithm Diagram Here During UI Integration]

Guideline References (Management)

National Osteoporosis Foundation

https://www.nof.org

Endocrine Society Guidelines

https://www.endocrine.org
These guidelines cover initiation thresholds, therapy selection, duration, and drug-holiday strategy.

11. Common Exam Traps

Bisphosphonates remain first-line in many patients.
Oral bisphosphonate administration requires remaining upright for 30 minutes.
Stopping denosumab abruptly can cause rebound vertebral fracture risk.
Teriparatide has a 2-year lifetime treatment limit.
Raloxifene increases venous thromboembolism risk.

12. Quick Revision Summary

Must Remember

  • T-score -2.5 or lower indicates osteoporosis
  • Weekly alendronate is a common first-line regimen
  • Denosumab is given every 6 months
  • Teriparatide is bone-anabolic therapy
  • Calcium plus vitamin D is foundational for all regimens

Practice Questions Placeholder

  • Topic: Osteoporosis and Bone Metabolism
  • Subtopics: bisphosphonates, denosumab, teriparatide, romosozumab, glucocorticoid-induced osteoporosis