Osteoporosis Flashcards
Bone Remodeling
• Osteoblasts—bone forming cells • Osteoclasts—bone resorbing cells • Osteocytes—bone communication cells Bone remodeling regulated by estrogens, androgens, vitamin D, parathyroid hormone (PTH), and others, including the cytokine RANK-ligand (RANKL) • Secondary hyperparathyroidism may also cause bone remodeling
Regulation of Remodeling
Bone Remodeling mediated by:
- Serum Ca
- Vitamin D
Life Style Risk Factors
- Low calcium/vitamin D intake
- Smoking
- Prior fractures
- Immobilization/low physical activity
- History of falls
- Low body weight
- Excess alcohol (≥ 2-3 per day)
Risk factors
Female, age, race •35% women ≥ 80 years of age • White/Hispanic > Native American > African American > Asian • 11% men ≥ 80 years of age
Conditions Risk factors
- Menopause (premature)
- Malabsorption
- RA and Lupus
- Fall risk conditions
- Vit D deficiency
- Cognitive impairment
- Height loss
- Family history
Medication Risk Factors
- Glucocorticoids - 5mg+ prednisone equivalent for 3+ months
- Anti-androgens
- Thyroid supplementation
- Antiepileptic drugs
- Aluminum
- PPIs
- Thiazolidinediones
Who to screen?
- All women by age 65
- All men over age 70
- All post-menopausal (PM) women ≥ 50 years
- Men age ≥ 50 years with risk factors
gold standard
- Central DXA X-ray gold standard
- Peripheral devices used for screening only
- Lumbar spine and hip (femoral neck, total hip)
- Reported as standard deviations (SD) from either:
- Matched population: Z-score
- “Normal”, young population: T-score
- Each SD = 10% ↓ bone mass, 1.5-2.5 x ↑ fracture risk
Risk Prediction: FRAX®
Used to predict fracture risk:
- Limited DXA access
- Determine DXA need
- NOT already treated
Diagnostic Criteria Osteopenia
Osteopenia (low bone mass)
T-score: -1 to -2.5
Diagnostic Criteria Osteoporosis
• T-score: -2.5 or less • Fragility fracture • Spine, hip, humerus, pelvis, or wrist • Independent of T-score • Osteopenia + elevated FRAX OR fragility fracture • 10-year probability ≥ 3 % for hip fracture • ≥ 20 % for major osteoporotic fracture
Normal bone density
T score +1 to -1
Osteoporosis Prevention and Treatment
• Calcium and Vit D
• Exercise, Smoking Cessation, Low Alcohol Intake, Fall Prevention,
Hip Protectors, Physical Therapy
Dosing & Formulations
- 1,000-1,200 mg/day (no more than 1,500 mg/day)
- < 600 elemental per dose (500 – 600 mg twice daily)
- Citrate in low acid
- No oyster shell!
% of Elemental Calcium in Supplements
Carbonate (40% elemental)
Citrate (21% elemental)
Gluconate (9% elemental)
Considerations
- ↑ Constipation = ↑ elemental Ca
- Kidney stones
- Dietary sources preferred
- QS dietary intake (average 600 mg/day)
- OP patients are high bone risk—Ca benefit outweighs any CV risk
Osteoclasts
Move from immature to mature cells
when their RANK receptor is
stimulated by the RANK-Ligand
RANKL inhibitors
Block maturation, activation, shorten lifespan of clasts, increase apoptosis
Calcitonin
Prevents clasts from adhering to bone
Bisphosphonates
Incorporate into bone to impair clast function and cause apoptosis
Estrogen and SERMs
Increase clast apoptosis, decrease RANK-Ligand
Osteoblasts function
Bone forming cells
PTH analogs affect on Osteoblasts
activate blasts
Estrogen and SERMs affect on Osteoblasts
decrease blast apoptosis
Sclerostin inhibitor
increases osteoblast activity
Denosumab is drug of choice for?
Denosumab—drug of choice for osteoporosis with renal insufficiency
Osteoporosis Treatment Algorithm First Line for Most
alendronate,
risedronate,
zoledronic acid,
denosumab
Osteoporosis Treatment for Low Risk (younger, no fractures, low mod T-score)
Oral Agents
ibandronate
alendronate,
risedronate
Treatment for Highest Fracture Risk (FRAX hip
>4.5% or major OP
>30%, multiple
fractures, T-score ≤ -3.0)
abaloparatide, denosumab, romosozumab, teriparatide, zoledronic acid
Treatment for High Risk Spine Fracture, low risk Hip or nonvertebral fractures
ibandronate or raloxifene
Does 1 fracture = therapy failure
1 fracture DOES NOT = therapy failure
• Suggest fracture risk is high
• May change treatment selection and/or duration
What is stable bone mineral density (BMD)
• Stable BMD = not worsened by more than ~4% in spine or ~6% in hip
Recheck BMD?
every 1-2 years after starting therapy and then every 2 years
Bisphosphonates for Postmenopausal Osteoporosis
- Alendronate Fosamax®,
- Ibandronate Boniva®,
- Risedronate Actonel®,Atelvia®
- Zoledronic acid (Reclast®) 5 mg IV every 2nd year 5 mg IV once yearly
Bisphosphonates Caution in renal impairment
at risk of dehydration, on diuretics or nephrotoxic drugs NR if CrCl < 35 mL/min
Duration of Bisphosphonate Use
• Risedronate VERT-MN trial (VERT-NA extension) DC at 3, 5 or 7 years BMD ↓ after DC BUT higher than baseline
•Alendronate FLEX trial (FIT-extension)
DC at 5 years vs. continuation to 10 years
BMD ↓ after DC BUT remained higher than baseline. No fracture differences……unless T-score at 5 years < -2.5 (2x higher!)
•Zoledronic Acid Horizon-PVT trial
DC at 3 or 6 years vs. continuation to 9 years. BMD ↓ after DC BUT remained higher than baseline No notable differences in fracture
Bottom Line on “Holidays”
- Lower Risk: Stop after 3 years (ZA) or 5 years (oral agents)
- Higher Risk: Continue for 6 years (ZA) or 10 years (oral agents)
- End holiday if fracture, significant BMD loss
Continuum of Bisphosphonates
3-5 Year Evaluation
RANK-L inhibitor: Denosumab
- 60 mg SQ in upper arm, thigh, abdomen every 6 months by a healthcare provider
- No drug holiday recommended
- Must correct Ca and Vit D before initiation 25-day half-life
- Drug of choice in renal impairment
PTH Analogs: Abaloparatide, Teriparatide
- Anabolic agents
- Use should be immediately followed by anti-resorptive therapy (bisphosphonate, denosumab)
- Use should not follow anti-resorptive therapy—lower BMD increases
- Must correct Ca and Vit D before initiation
- Nausea, orthostatic hypotension, leg cramps
- 2-year duration only
Sclerostin Inhibitor: Romosozumab
•210 mg once monthly (two consecutive 105 mg injections) in the upper arm, thigh, or abdomen by a healthcare professional
12 month duration
•Must correct hypocalcemia prior to use, supplement Ca and Vit D
•Boxed Warning—increased risk of MI, stroke, and CV death
Why Estrogens aren’t used
↑ fatal and nonfatal MI , stroke, VTE, breast cancer
Why Selective Estrogen Receptor Modulators aren’t used for Osteoporosis
↑ VTE
Stroke risk in women 70+: not recommended
Concomitant therapy is not recommended (exception: raloxifene and breast cancer reduction)
When to Stop Treating?
When to consider: • Prognosis & limited life expectancy • Goals of care • Immobility/low fall or fracture risk • Administration concerns • All can be stopped without taper
Osteoporosis: Clinical Pearls
•Upon dc of an anabolic agent, therapy with an antiresorptive agent is
recommended
• Switching from bisphosphonate to an anabolic agent can be done
• Switching from denosumab to an anabolic agent is NOT recommended
• Dietary calcium > supplement
