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2.7 Osteoporosis & Paget Disease of Bone

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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy

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2 Chapter 1: Cardiovascular Disease (14% of Exam)

1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection

3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)

2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia

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5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule

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6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease

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7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation

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9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria

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13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications

15 Chapter 14: Geriatric Syndromes (3% of Exam)

14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings

16 Chapter 15: Allergy & Immunology (2% of Exam)

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17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology

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19 Chapter 18: Perioperative Medicine & Medical Consultation

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20 Chapter 19: Ophthalmology (1% of Exam)

19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease

21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)

20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders

2.7 Osteoporosis & Paget Disease of Bone

Key Takeaways Explain This Topic AI

Osteoporosis is diagnosed by a T-score of -2.5 or below, by a fragility fracture regardless of density, or by a sufficiently elevated calculated fracture probability.

Denosumab must not simply be stopped, because discontinuation causes rapid rebound bone loss and multiple vertebral fractures unless another antiresorptive is started.

Anabolic agents are preferred initial therapy in very high fracture risk and must be followed by an antiresorptive to preserve the gain.

Paget disease typically presents as an isolated elevation of alkaline phosphatase with normal calcium and phosphate, and bisphosphonate therapy is the treatment of choice.

Vitamin D deficiency and osteomalacia are separately enumerated and must be corrected before antiresorptive therapy is started.

Last updated: August 2026

  • 1. Osteoporosis: Screening, Diagnosis & Pharmacotherapy
  • DEXA Interpretation & Diagnostic Criteria

Bone Mineral Density (BMD) is evaluated by Dual-Energy X-Ray Absorptiometry (DEXA):

T-Score (Standard deviations compared to peak bone mass of a healthy young sex-matched reference population):

  • Normal: T-score >= -1.0
  • Osteopenia (Low Bone Mass): T-score between -1.0 and -2.5
  • Osteoporosis: T-score <= -2.5 at lumbar spine, femoral neck, total hip, or 33% radius
  • Severe / Established Osteoporosis: T-score <= -2.5 PLUS >=1 fragility fracture

Clinical Diagnosis: A low-trauma / fragility fracture (fall from standing height or less) of the hip, vertebra, pelvis, or wrist in a postmenopausal woman or man >=50 years confirms osteoporosis regardless of the DEXA T-score .

Screening Indications (USPSTF, January 2025): Central DEXA of the total hip, femoral neck, or lumbar spine in all women >= 65 years (Grade B), and in postmenopausal women < 65 years who are at increased risk by clinical risk assessment (Grade B). The 2025 statement deliberately declines to set a numeric FRAX cut point; the older "8.4% major osteoporotic fracture risk" figure was an illustrative value for a 65-year-old woman, not a mandated threshold. In men , the USPSTF finds current evidence insufficient ( Grade I statement ), so male screening is driven by risk factors — glucocorticoid exposure, androgen deprivation therapy, hypogonadism, or a prior fragility fracture — rather than by age alone. Note that the >= 3.0% hip / >= 20% major osteoporotic FRAX figures are treatment thresholds for osteopenia, not screening thresholds ; conflating the two is a common exam trap.

Treatment Indications (NOF / Endocrine Society)

Initiate pharmacological therapy in postmenopausal women and men >=50 years with:

Hip or vertebral fragility fracture.

DEXA T-score <= -2.5 at femoral neck, total hip, or lumbar spine.

Osteopenia (T-score -1.0 to -2.5) WITH FRAX 10-year probability of hip fracture >= 3.0% OR major osteoporotic fracture >= 20.0% .

Pharmacotherapy: Antiresorptive vs. Anabolic Agents +-------------------------------------------------------------------------------------------------------------+

  • | DRUG CLASS / AGENT | MECHANISM & DOSING | CLINICAL EFFICACY & UNIQUE RISKS / PEARLS |
  • +------------------------------+-----------------------------+-----------------------------------------------+
  • | Oral Bisphosphonates | Inhibits osteoclastic | First-Line Therapy; |
  • | - Alendronate (70 mg weekly) | farnesyl pyrophosphate | Administration: Empty stomach, 8 oz plain |
  • | - Risedronate (35 mg weekly) | synthase; binds bone matrix | water, upright for >=30 min (pill esophagitis)|
  • | | | Contraindicated if eGFR < 35 mL/min; |
  • | | | Drug holiday after 3-5 years for moderate risk|
  • +------------------------------+-----------------------------+-----------------------------------------------+
  • | IV Bisphosphonates | Potent annual IV | Overcomes oral GI intolerance; |
  • | - Zoledronic Acid (5 mg IV) | bisphosphonate | Acute phase reaction (fever/myalgia in 30%); |
  • | | | Risks: Osteonecrosis of Jaw (ONJ), Atypical |
  • | | | Femoral Fractures (AFF with subtrochanteric |
  • | | | transverse cortical thickening / thigh pain) |
  • +------------------------------+-----------------------------+-----------------------------------------------+
  • | RANKL Inhibitor | Monoclonal antibody against | Safe in Chronic Kidney Disease (no renal dose |
  • | - Denosumab (60 mg SC q6m) | RANKL; prevents osteoclast | adjustment); |
  • | | differentiation & survival | CRITICAL WARNING: Discontinuation triggers |
  • | | | rapid rebound bone loss & MULTIPLE VERTEBRAL |
  • | | | FRACTURES! Must transition to bisphosphonate. |
  • +------------------------------+-----------------------------+-----------------------------------------------+
  • | Parathyroid Hormone Analogs | Intermittent PTH/PTHrP | Anabolic (stimulates bone formation); |
  • | - Teriparatide (PTH 1-34) | stimulation activates | Indicated for Severe Osteoporosis (T <= -3.0 |
  • | - Abaloparatide | osteoblasts > osteoclasts | or fragility fracture while on therapy); |
  • | | (20-80 mcg SC daily) | Max 2 years lifetime; Follow immediately with |
  • | | | bisphosphonate to lock in BMD gains |
  • +------------------------------+-----------------------------+-----------------------------------------------+
  • | Sclerostin Inhibitor | Monoclonal antibody against | Dual Anabolic + Antiresorptive effect; |
  • | - Romosozumab (210 mg SC/mo) | sclerostin (Wnt pathway) | Max 12 months duration; |
  • | | | Boxed Warning: Increased risk of MI and stroke|
  • | | | (Avoid if MI/stroke in preceding 12 months) |

+-------------------------------------------------------------------------------------------------------------+

  • 2. Secondary Osteoporosis, Glucocorticoid-Induced Bone Loss & Osteomalacia
  • Screening Every New Diagnosis for a Secondary Cause

Roughly 30% of postmenopausal women, and more than half of men and premenopausal women with osteoporosis, have an identifiable secondary cause. Finding it changes therapy, so obtain a focused panel before committing a patient to years of antiresorptive treatment: serum calcium, phosphorus, albumin, creatinine with eGFR, alkaline phosphatase, 25-hydroxyvitamin D , intact PTH, TSH, complete blood count, and a 24-hour urine calcium . Escalate to serum and urine protein electrophoresis with free light chains, tissue transglutaminase IgA, and an 8 a.m. total testosterone in men when bone loss is disproportionate to age or occurs at an unexpected site.

Secondary Cause Discriminating Clue Consequence for Management

Primary hyperparathyroidism High serum calcium with a high or inappropriately normal PTH; preferential cortical loss at the distal one-third radius Parathyroidectomy, not an antiresorptive, is the definitive treatment

Malabsorption / celiac disease Low 24-hour urine calcium (< 50 mg/day), low 25-hydroxyvitamin D, iron deficiency, high PTH Treat the enteropathy and replete vitamin D first

Multiple myeloma Anemia, wide protein gap, discrete lytic lesions rather than diffuse osteopenia Oncologic therapy; bisphosphonate is adjunctive

Idiopathic hypercalciuria 24-hour urine calcium > 250-300 mg/day, nephrolithiasis Thiazide reduces calcium excretion and preserves bone

Hyperthyroidism or over-replacement Suppressed TSH, including from an excessive levothyroxine dose Reduce the levothyroxine dose before adding a bone agent

Hypogonadism Amenorrhea, low testosterone, aromatase inhibitors, androgen deprivation therapy Bone agent alongside the required cancer therapy

Chronic kidney disease eGFR < 35 mL/min, high PTH, high phosphate Bisphosphonates contraindicated; denosumab needs no renal adjustment but causes severe hypocalcemia in advanced CKD

Drugs Glucocorticoids, aromatase inhibitors, androgen deprivation, anticonvulsants, long-term heparin, thiazolidinediones Mitigate or substitute where clinically possible

Glucocorticoid-Induced Osteoporosis (2022 ACR Guideline)

Glucocorticoid-induced osteoporosis is the most common form of drug-induced bone disease, and it behaves differently from postmenopausal osteoporosis in two ways the exam tests directly. First, bone loss is biphasic — a rapid trabecular loss of roughly 6-12% during the first year, then a slower ongoing loss of about 3% per year. Second, fractures occur at a higher bone mineral density than in postmenopausal osteoporosis , because glucocorticoids degrade bone quality (osteoblast and osteocyte apoptosis, suppressed bone formation, reduced intestinal calcium absorption, and hypogonadism) rather than only bone quantity. A reassuring T-score therefore does not exclude significant fracture risk in a steroid-treated patient.

Whom to assess: every adult starting or continuing a prednisone-equivalent dose of >= 2.5 mg/day for more than 3 months . For patients aged >= 40 years, assess with FRAX plus DEXA and vertebral fracture assessment ; reassess every 1-2 years on continued therapy.

FRAX correction: for prednisone-equivalent doses > 7.5 mg/day , multiply the FRAX 10-year major osteoporotic fracture risk by 1.15 and the hip fracture risk by 1.2 , because FRAX assumes only a moderate steroid dose.

Very high fracture risk is defined by any of: a prior osteoporotic fracture, a T-score <= -3.5 , a glucocorticoid-adjusted FRAX major osteoporotic risk >= 30% or hip risk >= 4.5% , or high-dose exposure ( >= 30 mg/day for more than 30 days , or a cumulative annual dose >= 5 g ).

Everyone on chronic glucocorticoids receives optimized calcium ( 1,000-1,200 mg/day , diet preferred) and vitamin D ( 600-800 IU/day , more if deficient), weight-bearing exercise, smoking cessation, alcohol limitation, and fall-risk reduction — plus use of the lowest effective steroid dose for the shortest necessary duration.

Moderate, high, and very high risk patients receive pharmacologic therapy, choosing among oral or intravenous bisphosphonates, denosumab, or a parathyroid hormone analog by shared decision-making. Anabolic agents are conditionally preferred as initial therapy at high and very high risk. Denosumab is a reasonable choice when a bisphosphonate is contraindicated, but it carries the same absolute prohibition on abrupt discontinuation described above.

Osteomalacia and Severe Vitamin D Deficiency

Osteomalacia is defective mineralization of newly formed osteoid in the mature skeleton ; rickets is the same defect occurring before physeal closure. The conceptual distinction that drives exam questions is that osteoporosis is too little normally mineralized bone, whereas osteomalacia is a normal or even increased volume of poorly mineralized bone. The two look similar on DEXA — both give a low T-score — but they are biochemically and therapeutically opposite.

Causes: severe vitamin D deficiency (malabsorption after bariatric surgery, celiac disease, chronic pancreatitis, minimal sun exposure with dark skin or full covering), chronic kidney disease, anticonvulsants that induce vitamin D catabolism (phenytoin, phenobarbital, carbamazepine), aluminum-containing antacids, and renal phosphate wasting from X-linked hypophosphatemia or tumor-induced osteomalacia caused by an FGF23-secreting mesenchymal tumor.

Clinical picture: diffuse, dull bone pain and bony tenderness — in sharp contrast to the painless bone loss of uncomplicated osteoporosis — plus a proximal myopathy with a waddling gait and difficulty rising from a chair or climbing stairs, and low-trauma fractures.

Biochemistry: low or low-normal calcium, LOW phosphate, ELEVATED alkaline phosphatase, ELEVATED PTH (secondary hyperparathyroidism), and a 25-hydroxyvitamin D usually below 10-15 ng/mL. Osteoporosis, by contrast, has an entirely normal panel — a normal alkaline phosphatase is one of the fastest ways to separate them.

Radiographic hallmark: Looser zones (pseudofractures) — transverse lucent bands running perpendicular to the cortex at the medial femoral neck, pubic rami, ribs, and lateral scapula.

Treatment: replete vitamin D (for example ergocalciferol 50,000 IU weekly for 8-12 weeks, then maintenance), correct calcium and phosphate, and treat the underlying malabsorption or phosphate-wasting lesion. Correct deficiency before starting a potent antiresorptive — giving intravenous zoledronic acid or denosumab to a vitamin D-deficient patient precipitates severe symptomatic hypocalcemia with tetany and QT prolongation.

Monitoring, Drug Holidays & Agent Sequencing

Repeat central DEXA at 1-2 year intervals after starting or changing therapy, and use the same machine — cross-machine comparisons are not valid. Bone turnover markers (serum CTX for resorption, P1NP for formation) are used mainly to confirm adherence and biological response.

Treatment failure means a fragility fracture after the first year of therapy or a significant BMD decline on treatment. Respond by verifying adherence and administration technique, re-screening for a missed secondary cause, and escalating to a different class rather than simply continuing.

A drug holiday applies only to bisphosphonates , which persist in the skeleton after they are stopped. Reassess after 5 years of oral or 3 years of intravenous therapy: patients back at moderate risk may pause, while those still at high risk continue to 10 years oral or 6 years intravenous. There is no drug holiday for denosumab, romosozumab, teriparatide, or abaloparatide.

Sequencing matters. Giving an anabolic agent first and following with an antiresorptive produces substantially larger density gains than the reverse order, because prior bisphosphonate exposure blunts the anabolic response. Never allow a course of an anabolic agent or of denosumab to simply end — an antiresorptive must follow to lock in the gain.

  • 3. Paget Disease of Bone (Osteitis Deformans)
  • Paget Disease of Bone (Osteitis Deformans)

Pathophysiology: Focal skeletal disorder characterized by excessive, disorganized osteoclastic bone resorption followed by chaotic, irregular osteoblastic bone deposition, resulting in expanded, structurally weak, hypervascular "woven bone" with a mosaic pattern on histology.

Clinical Presentation: Often asymptomatic with an isolated elevation of Alkaline Phosphatase (ALP) (with normal serum calcium, phosphorus, and liver transaminases). Symptomatic patients present with bone pain, bowing of long bones (saber shins), increased hat size (skull enlargement), conductive/sensorineural hearing loss (temporal bone involvement), warmth over affected bones, and high-output congestive heart failure (from massive skeletal AV shunts). Malignant degeneration into Osteosarcoma occurs in <1% (suspect if sudden worsening localized bone pain and swelling).

Radiological Findings: Osteolytic wedge ("blade of grass" / "flame sign"), cortical thickening, expansion of bone, and classic "cotton wool" skull appearance.

Treatment of Choice: Intravenous Zoledronic Acid (5 mg IV single infusion) , which produces rapid, prolonged biochemical remission and pain relief.

Establishing Extent and Deciding Whom to Treat

Paget disease is the second most common metabolic bone disease after osteoporosis, is rare before age 55, and clusters in families — germline SQSTM1/p62 mutations are found in a substantial minority of familial cases. Once the biochemical and radiographic picture is recognized, two further steps complete the workup:

Confirm that the alkaline phosphatase elevation is skeletal. A normal gamma-glutamyl transferase and normal transaminases point to bone; when liver disease coexists, order a bone-specific alkaline phosphatase . Serum calcium and phosphate are characteristically normal — hypercalcemia appears only when an extensively affected patient is immobilized, which should prompt a search for a coexisting cause such as primary hyperparathyroidism.

Map the skeleton with a radionuclide bone scan. Pagetic lesions are intensely tracer-avid, and the scan finds clinically silent sites that plain films of the painful area will miss. Each abnormal site is then imaged with a plain radiograph to confirm the characteristic appearance and to exclude a metastasis, which the bone scan cannot distinguish on its own.

Indications for bisphosphonate therapy are symptomatic disease — most often bone pain — and asymptomatic disease at sites where complications are likely: the skull (hearing loss, cranial neuropathy), weight-bearing long bones (bowing, pathologic fracture), vertebrae (spinal stenosis, cord compression), and bone adjacent to a major joint (secondary osteoarthritis). Treatment is also given before elective orthopedic surgery on pagetic bone , because reducing the marked hypervascularity substantially lowers intraoperative blood loss. Purely asymptomatic disease at a low-risk site such as the ilium may simply be monitored.

Monitoring and re-treatment: recheck alkaline phosphatase at 3 and 6 months after the infusion. Normalization signals biochemical remission, which after zoledronic acid commonly lasts several years. Re-treat when the alkaline phosphatase rises again in combination with recurrent symptoms, rather than for an isolated biochemical drift. Ensure calcium and vitamin D are replete before the infusion to prevent post-dose hypocalcemia.

Complications to recognize: pathologic fracture through weakened woven bone, secondary osteoarthritis of the hip or knee adjacent to a deformed bone, spinal stenosis and nerve root or cord compression, conductive and sensorineural hearing loss from temporal bone involvement, high-output heart failure from skeletal arteriovenous shunting in extensive disease, and osteosarcoma in fewer than 1% — suspected when established Paget disease develops abrupt new localized pain with a soft-tissue mass. Teriparatide and other parathyroid hormone analogs are contraindicated in Paget disease because of osteosarcoma risk.