Osteoporosis & Bone Physiology Lecture

A set of 50 question-and-answer flashcards covering bone physiology, osteoporosis pathology, and pharmacologic treatments.

What are the four principal functions of bone?

Support, movement (lever attachment for muscles), reservoir of ions (Ca2+, phosphate, Mg2+, Na+), and housing the hematopoietic system.

Which two major types of bone make up the skeleton and which is more metabolically active?

Cortical (compact) bone and trabecular (cancellous) bone; trabecular bone is more metabolically active.

From which progenitor cells are osteoblasts derived?

Mesenchymal stem cells.

What is the primary role of an osteoblast?

To build bone by depositing collagen matrix and mineralizing it.

Which signaling pathway stimulates osteoblasts and which molecule inhibits them?

Wnt/β-catenin stimulates osteoblasts, while sclerostin inhibits them.

Approximately what percentage of osteoblasts normally undergo apoptosis?

About 60–80 %.

Osteoclasts arise from the fusion of precursors in which cell lineage?

Monocyte/macrophage lineage.

Which receptor–ligand pair drives osteoclast differentiation?

RANK on precursors interacting with RANKL.

What protein produced by osteoblasts acts as a decoy receptor for RANKL?

Osteoprotegerin (OPG).

Name two positive regulators of osteoclast formation besides RANKL.

M-CSF and reactive oxygen species (ROS).

What are osteocytes and which inhibitor of bone formation do they secrete?

Mature osteoblasts embedded in bone matrix; they secrete sclerostin.

Outline the basic sequence of events in bone remodeling.

Pre-osteoblasts secrete RANKL → osteoclast precursors fuse/activate → bone resorption → osteoblasts follow, lay collagen, mineralize → some osteoblasts become osteocytes.

Why does bone mass generally decline with aging?

Each remodeling cycle leaves a small deficit in bone formation, which accumulates over time.

Differentiate osteoporosis from osteopenia.

Both involve bone loss, but osteoporosis represents greater bone loss and higher fracture risk than osteopenia.

Does fracture risk depend solely on bone mineral density (BMD)?

No—BMD is important but fracture risk also depends on skeletal strength and other factors.

Give two endocrinopathies that can cause secondary osteoporosis.

Examples: thyrotoxicosis and primary hyperparathyroidism.

Name two medications that can lead to secondary osteoporosis.

Chronic glucocorticoids and androgen-deprivation therapy with GnRH agonists.

Identify two gastrointestinal or nutritional causes of secondary osteoporosis.

Vitamin D deficiency and celiac sprue.

List two ‘other’ disease states associated with secondary osteoporosis.

Alcoholism and rheumatoid arthritis (others include COPD, multiple myeloma, etc.).

What are the four broad pharmacologic categories used to treat osteoporosis?

Bisphosphonates, calcium balance agents (Ca2+, Vitamin D, calcitonin, PTH analogs), SERMs/estrogen, and biologics.

Bisphosphonates are structural analogs of which endogenous molecule?

Pyrophosphate.

How do bisphosphonates reach osteoclasts to exert their effect?

They incorporate into the bone matrix and are released when bone is resorbed by osteoclasts.

What specific effect do bisphosphonates have on the osteoclast’s ruffled border?

They impair formation of the ruffled border, reducing the cell’s ability to resorb bone.

Nitrogen-containing bisphosphonates inhibit which enzyme in the cholesterol synthesis pathway?

Farnesyl pyrophosphate synthase.

Why might IV nitrogenous bisphosphonates trigger an acute-phase reaction?

Accumulation of isopentenyl pyrophosphate increases TNF-α levels.

How do non-nitrogen bisphosphonates inhibit osteoclasts?

They are metabolized into ATP analogs that create non-functional ATP, leading to osteoclast apoptosis.

State three common disadvantages or GI-related ADRs of oral bisphosphonates.

Poor absorption (1–5 %), need for empty stomach dosing, and risks of reflux, esophagitis, or gastric ulcers.

What rare but serious jaw complication is associated with bisphosphonate therapy?

Osteonecrosis of the jaw.

What are three potential adverse effects of high-dose calcium supplementation?

Hypercalcemia, hypercalciuria, and nephrolithiasis.

What is the mechanism of action of teriparatide?

Intermittent activation of the PTH receptor stimulates osteoblast progenitors, producing an anabolic effect on bone.

Which bone compartment gains more mass with teriparatide therapy?

Trabecular bone.

For how long is teriparatide therapy recommended due to the potential osteosarcoma risk?

No more than 2 years.

Raloxifene and bazedoxifene are members of which drug class?

Selective estrogen receptor modulators (SERMs).

How does raloxifene reduce osteoclast activity?

By inducing osteoprotegerin, which lowers osteoclast number and activation.

What major vascular adverse event is a known risk with SERMs?

Venous thromboembolism (e.g., deep-vein thrombosis).

Denosumab targets which molecule to exert its anti-resorptive effect?

It is a monoclonal antibody against RANKL.

What happens to bone mineral density when denosumab therapy is stopped abruptly?

Rapid BMD loss and increased fracture risk.

What is romosuzumab’s mechanism of action?

It is an antibody to sclerostin, removing inhibition of osteoblasts and producing an anabolic effect.

Why is romosuzumab limited to 12 monthly doses?

Potential risks (e.g., MI, stroke) and the need to follow with an anti-resorptive agent.

Name two anabolic agents used in osteoporosis therapy.

Teriparatide/abaloparatide and romosuzumab.

Name two major anti-resorptive drug classes for osteoporosis.

Bisphosphonates and denosumab.

Which bone type provides rigidity and which provides elasticity?

Cortical bone provides rigidity; trabecular bone provides elasticity.

Which bone type predominates in the axial skeleton and at the ends of long bones?

Trabecular (cancellous) bone.

Which osteocyte-derived protein inhibits osteoblast activity?

Sclerostin.

What is the decoy receptor secreted by osteoblasts that neutralizes RANKL?

Osteoprotegerin (OPG).

How do chronic glucocorticoids elevate fracture risk?

They decrease osteoblast activity and increase bone resorption, leading to rapid bone loss.

Why must oral bisphosphonates be taken on an empty stomach?

They have very low bioavailability (1–5 %) and food further impairs absorption.

Which cardiovascular adverse events have been linked to romosuzumab therapy?

Myocardial infarction and stroke.

Which common supplement used in osteoporosis prevention can increase kidney stone risk?

Calcium (especially when combined with high-dose Vitamin D).

How does inhibition of farnesyl pyrophosphate synthase by nitrogenous bisphosphonates suppress osteoclast function?

It blocks protein prenylation, disrupting osteoclast cytoskeleton and ruffled border formation, thereby halting bone resorption.