Osteoporosis Pharmacotherapy Practice Flashcards

Comprehensive practice flashcards covering drug classes, mechanisms of action, administration, and adverse effects for osteoporosis pharmacotherapy as presented in the lecture notes.

Major classes of osteoporosis pharmacotherapy

Bisphosphonates; denosumab; raloxifene (SERM); teriparatide and abaloparatide (anabolic agents); romosozumab (sclerostin inhibitor); calcium + vitamin D as supportive therapy.

First-line pharmacotherapy for osteoporosis

Bisphosphonates: alendronate, risedronate, and zoledronic acid.

Mechanism of Action (MOA) of bisphosphonates

Bind to bone mineral and inhibit osteoclast function $\rightarrow \text{decreased bone resorption}$.

Common oral bisphosphonates

Alendronate, risedronate, and ibandronate.

Zoledronic acid

A bisphosphonate commonly administered IV once yearly.

Administration instructions for oral alendronate

Take on an empty stomach with plain water; remain upright for at least $30\text{ minutes}$; avoid food and other medications during that interval.

Major GI adverse effect of oral bisphosphonates

Esophagitis / esophageal irritation.

Rare long-term complications of bisphosphonates

Osteonecrosis of the jaw (ONJ) and atypical femoral fractures.

Acute-phase reaction

A potential adverse effect after IV zoledronic acid characterized by fever, myalgia, arthralgia, and flu-like symptoms.

RANKL inhibitor

Denosumab.

Mechanism of Action (MOA) of denosumab

Monoclonal antibody against RANKL $\rightarrow \downarrow \text{osteoclast formation and activity} \rightarrow \downarrow \text{bone resorption}$.

Denosumab administration

$60\text{ mg}$ subcutaneously every $6\text{ months}$.

Risks of abrupt denosumab discontinuation

Rebound increase in bone turnover $\rightarrow$ rapid bone loss $\rightarrow$ increased risk of multiple vertebral fractures.

Hypocalcemia

An important electrolyte abnormality that can occur with denosumab.

Major anabolic osteoporosis drugs

Teriparatide and abaloparatide.

Effect of intermittent teriparatide

Intermittent PTH-receptor stimulation $\rightarrow \uparrow \text{osteoblast activity} \rightarrow \uparrow \text{bone formation}$.

Clinical indication for anabolic agents

Patients at very high fracture risk, such as those with severe osteoporosis or multiple/high-risk fractures.

Post-anabolic therapy protocol

Generally followed by an antiresorptive agent, such as a bisphosphonate or denosumab, to help maintain BMD gains.

Romosozumab

A sclerostin inhibitor that increases bone formation and decreases bone resorption.

Romosozumab administration

Monthly subcutaneous injections for a maximum of $12\text{ months}$.

Romosozumab safety concern

Potential cardiovascular risk; avoid/use caution in patients with recent MI or stroke.

Raloxifene

A selective estrogen receptor modulator (SERM) with estrogen agonist effects in bone.

Primary fracture reduction of raloxifene

Vertebral fractures.

Venous thromboembolism (VTE)

A major adverse effect associated with raloxifene; hot flashes can also occur.

Role of calcium and vitamin D

Supportive measures; usually not adequate alone as treatment for established osteoporosis.

Primary antiresorptive drugs

Bisphosphonates, denosumab, and raloxifene.

Bone-forming/anabolic drugs

Teriparatide and abaloparatide; Romosozumab also has anabolic effects.

Bisphosphonate simplified effect

$\downarrow \text{Osteoclast} \rightarrow \downarrow \text{bone resorption}$.

Denosumab simplified effect

$\text{RANKL blocker} \rightarrow \downarrow \text{osteoclast activity}$.

Teriparatide simplified effect

$\text{PTH analog} \rightarrow \uparrow \text{osteoblast activity} \rightarrow \uparrow \text{bone formation}$.

Romosozumab simplified effect

$\text{Sclerostin inhibitor} \rightarrow \uparrow \text{bone formation} + \downarrow \text{bone resorption}$.

Denosumab safety warning

Do not stop abruptly due to risk of rapid bone loss and fractures.

Oral bisphosphonates (alendronate/risedronate) common warning

Associated with esophagitis.

Raloxifene safety warning

Associated with increased risk of Venous thromboembolism (VTE).

Romosozumab safety warning (Clinical)

Contains a cardiovascular warning.

Alternatives for oral bisphosphonate intolerance

IV zoledronic acid or denosumab, depending on renal function, calcium status, and fracture risk.