Metabolic Bone Diseases

Flashcards testing core concepts, facts, diagnostics, treatments, and diagnostic thresholds for metabolic bone diseases including osteoporosis, osteomalacia, rickets, hyperparathyroidism, and CKD-MBD.

What is the primary underlying pathophysiology of osteoporosis?

An imbalance between bone resorption and bone formation, leading to bone loss, structural decay of the skeleton, and enhanced bone fragility with an increased risk of fracture.

What are the common anatomical sites affected by osteoporotic fractures?

Spine (causing acute pain, kyphosis, and loss of height), hip (femoral neck, intertrochanter), distal end of radius, and proximal humerus.

What is the 1-year mortality rate following an osteoporotic hip fracture?

$$20\text{--}24\%$$

What percentage of patients become totally dependent following a hip fracture?

$$33\%$$

According to meta-analysis data, operating on hip fracture patients within $48\text{ hours}$ reduces 12-month mortality risk by what amount?

A $20\%$ lower risk of dying within $12\text{ months}$ ($RR = 0.80$, $95\% CI = 0.66\text{--}0.97$) and fewer complications ($8\%$ vs $17\%$).

What is the target $INR$ level prior to hip fracture surgery for patients taking anticoagulant therapy (warfarin)?

$$INR \le 1.5$$

In the bone resorption pathway, how does estrogen affect the RANK-RANKL-OPG pathway?

Estrogen increases $\beta\text{-catenin}$, which increases Osteoprotegerin ($OPG$) and decreases $RANKL$.

Which protein acts as an inhibitor to osteoblast differentiation in the Wnt signaling pathway?

Sclerostin

What dose and duration of systemic glucocorticoid therapy is associated with secondary osteoporosis?

Daily prednisolone $5\,mg$ or equivalent for at least $3\text{ consecutive months}$.

What Body Mass Index ($BMI$) threshold is considered a modifiable risk factor for osteoporosis?

$$BMI < 20\,kg/m^2$$

When is peripheral BMD of the $33\%$ radius indicated during a DXA scan?

When an obese patient weighs $> 130\,kg$ or when axial BMD cannot be assessed.

What is the WHO DXA T-score definition for Osteoporosis in menopausal women or men aged $\ge 50\text{ years}$?

A BMD T-score of $\le -2.5\,SD$ at the lumbar spine, femoral neck, or total hip.

How is BMD interpreted using DXA Z-scores in premenopausal women or men under $50\text{ years}$?

A Z-score $\le -2.0\,SD$ is classified as 'Below the expected range for age', and a Z-score $> -2.0\,SD$ is classified as 'Appropriate or within the expected range for age'.

What is the recommended daily calcium intake and upper limit for postmenopausal women and adults aged $> 50\text{ years}$ according to the Thai Osteoporosis Foundation Guideline (2021)?

Recommended intake is $1,000\,mg/day$ with an upper limit of $2,000\,mg/day$.

What is the percentage of elemental calcium and primary characteristic of Calcium carbonate?

It contains $40\%$ elemental calcium and is the most common and least expensive formulation, but can cause constipation.

Why is calcium acetate preferred for patients with Chronic Kidney Disease (CKD)?

It provides good phosphate binding with less aluminum absorption.

Which calcium formulation contains $20\%$ elemental calcium and is the formulation of choice in achlorhydria, IBD, and absorption disorders?

Calcium citrate

What are the two inactive forms of vitamin D and their sources?

Cholecalciferol (vitamin D3) from sunlight and animal/fish sources, and Ergocalciferol (vitamin D2) from mushrooms and yeast.

How is serum $25(OH)D$ status classified according to US Endocrine Society/AACE guidelines?

Deficiency is $< 20\,ng/mL$, Insufficiency is $20\text{--}30\,ng/mL$, Sufficiency is $> 30\text{--}100\,ng/mL$, and Toxic is $> 100\,ng/mL$.

What is the recommended weekly Vitamin D2 supplementation dosage for baseline serum $25(OH)D < 20\,ng/mL$?

$$60,000\,IU/week$$

Which dementia subtype has the highest prevalence of falls ($90\%$)?

Parkinson's disease dementia

What FRAX 10-year probability threshold for hip fracture warrants pharmacologic treatment in patients with osteopenia?

A 10-year probability for hip fracture $\ge 3\%$.

What is the molecular mechanism of action of bisphosphonates?

Inhibition of farnesyl pyrophosphate synthase ($FPPS$) in the mevalonate pathway of the osteoclast, leading to osteoclast apoptosis.

What GFR limits contraindicate the use of alendronate and zoledronic acid?

Chronic kidney disease with $GFR < 35\,mL/min$.

What are the two primary long-term adverse effects of bisphosphonates?

Atypical femoral fracture (AFF) and bisphosphonate-related osteonecrosis of the jaw (BRONJ).

Why must a patient be switched to a bisphosphonate before terminating Denosumab therapy?

To prevent a rebound effect of fractures.

What is the maximum duration of treatment for Teriparatide (Forteo)?

$$2\text{ years}$$

What cardiovascular contraindication applies to Romosozumab?

Romosozumab should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year.

What classical radiographic features on X-ray define osteomalacia?

Pseudofractures or Looser zones (radiolucent areas from microstress fractures) and fish-tail vertebrae (biconcave vertebral bodies).

What laboratory findings are typical for rickets and osteomalacia?

Hypocalcemia, hypophosphatemia, increased serum alkaline phosphatase, hypovitaminosis D, and secondary hyperparathyroidism.

What is the most common cause of primary hyperparathyroidism?

A single parathyroid adenoma (found in $80\%$ of patients).

What is 'Rugger-Jersey spine' in hyperparathyroidism?

Osteosclerosis of the vertebral endplates seen on X-ray.

What is a Brown tumor in hyperparathyroidism?

An osteitis fibrosa cystica lesion where PTH stimulates osteoclastic activity, replacing bone with vascularized fibrous tissue that appears on X-ray as an expansile, lytic, well-defined, non-sclerotic lesion.

What sequence of physiological events occurs in CKD-MBD leading to secondary hyperparathyroidism?

Phosphate retention increases $FGF23$ and decreases $1,25(OH)_2D$, which leads to hypocalcemia and a secondary increase in $PTH$.