Metabolic Bone Diseases: 1 Flashcards
Metabolic bone diseases
5
- Osteoporosis
- Paget disease of the bone
- Osteomalacia
- Rickets
- Renal osteodystrophy
- What is the most common bone disease in the US?
2. Osteoporosis PP?
- Most common metabolic bone disease in the US
- Imbalance of bone homeostasis
- Bone resorption (osteoclast activity) outpaces bone deposition (osteoblast activity)
Bone remodeling: Continuous process and regulated by 2 control loops. Describe these? 2
- Negative feedback loop
- Hormonal process that maintains calcium homeostasis - Stress on the skeleton
- Mechanical
- Gravitational
Describe the hormonal control of bone homeostasis with PTH
3 steps
- Decrease in plasma calcium
- Release of PTH from the parathyroid
- Kidney, bones, GI
Effects of PTH
- Kidney? 2
- Bone? 2
- GI tract? 1
- ↑ Ca resorption in the renal tubules
- Kidneys convert Vit D to it’s active form
- ↑ osteoclast activity
- Release Ca2+ and PO4-
- GI tract ↑ absorption of Ca2+, PO4-
What is responsible for bone reabsorption?
Osteoclast activity
Osteoclast activity
Stimulated by? 4
- PTH,
- Calcitonin,
- GF IL-6
- Lack of gonadal hormones
Osteoclast activity
Lack of gonadal hormones affects the body how? 2
- Increased activity, vigor and lifespan of clasts
2. Low estrogen increases IL-6
Osteoblast activity
- Affect bone matric how?
- How do osteoblasts change with age?
- Builders of bone matrix
2. Decreased number of osteoblasts with aging
Thyroid gland: can stimulate or inhibit osteoclast activity
- How would it increase?
- Decrease it?
- Hyperthyroidism
- Thyroid hormones can stimulate osteoclast activity - ↑ plasma calcium
- Thyroid gland releases calcitonin
Hormonal control of bone homeostasis with Ca? 3 steps
- Increased Ca2+
- Calcitonin released from the thyroid
- Kidney, bones, GI tract
Effects of calcitonin
- Kidney? 2
- Bones? 2
- GI? 1
- ↓Ca2+ absorption
- ↓PO4- absorption
- ↓ osteoclast activity
- ↓ release of Ca2+
- ↓ Ca2+ absorption
Risk factors (major categories) OP 9
- Age (≥ 50 years old)
- Gender (female)
- Race (white or Asian)
- Activity level (inactivity)
- Diet
- Hormonal
- Meds
- Family history
- Medical history
Dietary risk factors for OP? 3
- ETOH
- Tobacco
- Low calcium intake or altered ability to absorb
Hormonal risk factors for OP? 6
- Amenorrhea
- Late menarche
- Early menopause
- Post menopausal state
- Low testosterone
- Low estrogen
Medical conditions that may be associated with osteoporosis
9
- Rheumatologic conditions (Lupus, RA, others)
- Malabsorption syndromes
- Hypogonadism
- Hyperthyroidism
- Chronic kidney disease
- Chronic liver disease
- COPD
- Hyperthyroidism
- Neurologic disorders
Meds that put you at risk for OP?
12
- Heparin
- Warfarin +/-
- Cyclosporine
- Medroxyprogesterone acetate (Provera)
- Vitamin A
- Loop diuretics
- Chemotherapeutic drugs
- Antiseizure meds
- Proton pump inhibitors
- H2 Blockers
- Antidepressants (TCA’s and SSRI’s)
- Glucocorticoids (STEROIDS)
Mnemonic
OSTEOPOROSIS
12
- LOw calcium intake
- Seizure meds
- Thin build
- ETOH
- HypOgonadism
- Previous fracture
- ThyrOid excess
- Race (white, Asian)
- Other relatives with osteoporosis
- Steroids
- Inactivity
- Smoking
Prevention of osteoporosis
5
- Exercise (weight bearing and muscle strengthening)
- Appropriate vitamin D and calcium intake
- Cessation of tobacco use
- Avoidance of excessive alcohol intake
- Screening tests: Measure height, DXA
Standard test for the evaluation of bone mineral density?
DEXA (DXA) scan
DEXA scan: Max weight for the machine?
300 pounds (some newer machines support up to 400 pounds)
DEXA (DXA) scan indications
3
- Anyone currently being treated or considering pharmacologic therapy for osteoporosis
- Anyone not receiving therapy in whom evidence of bone loss would lead to treatment
- Screening for osteoporosis
DEXA (DXA) scan: Screening guidelines
5
- All women ≥ 65 and men ≥ 70 regardless of risk factors
- Younger postmenopausal women and men (50-70 years) with risk factors
- Adults with fragility fractures
- Adults who have a condition associated with low bone mass (rheumatoid arthritis)
- Adults who take medications associated with bone loss (steroids)
What is your T score?
Bone mineral density compared to what is normally expected in a young healthy adult (at their peak BMD) based on gender.
- Osteopenia T score?
- Osteoporosis?
- Severe osteoporosis?
- -1 to -2.5
- Less than -2.5
- Less than -2.5 plus fragility fracture(s)
Z-score is different than the T-score
Used in the following populations? 3
- Premenopausal women
- Men younger then 50 years
- Children
Z score
- -2.0 or lower?
- Above -2.0?
Dx of osteoporosis in this group should not be based on BMD results alone
- -2.0 or lower
defined as “below the expected range for age” - Above -2.0
“within the expected range for age”
Quantitative calcaneal ultrasonography
- Effective at predicting what?
- Advantages? 3
- Used for what?
- Effective at predicting
- femoral neck,
- hip and
- spine fractures - Lower cost than DXA
- Portable
- No exposure to radiation
- Used as a screening test not for diagnosis of osteoporosis
Screening: Vertebral imaging (NOF recommendations)
1. If bone density testing is not available? 2
- Consider in patients with T-score -1.5 in? 3
- If bone density testing is not available
- All women ≥ 70
- All men ≥ 80 - Consider in patients with T-score -1.5
- Women 65-69
- Men 75-79
- Once the initial test is done repeat if suspect new vertebral fracture, loss of height or new back pain or postural change
When should you repeat the vertebral imaging? 4
repeat if suspect
- new vertebral fracture,
- loss of height or
- new back pain or
- postural change
Screening: Vertebral imaging (NOF recommendations)
6
- Postmenopausal women 50-64 and
- men 50-69 with specific risk factors
- Low trauma fx,
- historical height loss of 1.5” or more,
- prospective height loss of 0.8” or more,
- recent or ongoing long term glucocorticoid treatment
Osteoporosis Work up
5
- History
- Physical exam
- Lab
- +/- X-rays
- DXA scan
OP Hx questions?
4
- Include questioning to determine if there is any history of disease that may affect bone metabolism
- Family history
- Any history of low vitamin D, prior bone density testing, prior fractures
- Medication review
OP signs and symptoms? 3
- Usually asymptomatic unless there is a fracture.
- Gradual loss of height
- Dowager’s hump
OP Work up continued: Lab
8
- CBC
- CMP
- Serum magnesium
- TSH
- 25-OH Vitamin D
- PTH
- Testosterone (in younger men)
- 24 H urine calcium
Work up: X-rays
- For who?
- In asymptomic pts with?
- Cannot be used to dx?
- In symptomatic patients
- In asymptomatic patients if a vertebral fracture is suspected (or recent loss of height)
- Cannot be used to diagnose osteoporosis but can suggest osteopenia
Nonpharmacologic Treatment
3
- Calcium
- Vitamin D
- Exercise
Ca2+
1200 mg daily (from diet and supplements)
SE? 4
Side effects
- Nephrolithiasis
- Dyspepsia
- Constipation
- Interfere with the absorption of iron and thyroid hormone
Calcium citrate vs. calcium carbonate
- Calcium citrate when?
- Also less likely to cause what?
- When concomitant use of acid suppressing meds (H2 blockers and PPIs)
- Citrate is better absorbed - Citrate may be less likely to cause kidney stones
Vitamin D
800 IU vitamin D3 supplementation daily is recommended
SE? 3
May need more if initial vit D levels are low
Side effects Excessive vit D levels can cause 1. hyperpcalcemia, 2. hypercalciuria, 3. kidney stones
NOF 2014 guidelines for pharmacologic treatment
6
1. Age 50 and older and 2. Hip or vertebral fracture or 3. T-scores ≤ -2.5 (measured at femoral neck, total hip or lumbar spine)
- T-score
- 1.0 to -2.5 in postmenopausal women and men age 50 and older - Plus 10 year hip fx probability ≥ 3%
- or a 10 y major osteoporosis fracture probability of ≥ 20%
Pharmacologic options for treatment of osteoporosis
7
- Bisphosphonates
- Calcitonin
- Estrogen agonist/antagonist (raloxifene, Evista)
- Hormone therapy
- Parathyroid hormone 1-34 (teriparatide)
- RANKL inhibitor (denosumab)
- Tissue selective estrogen complex (conjugated estrogens/bazedoxifene, Duaveetm)
Bisphosphonates
Which drugs are these? 4
- Alendronate (Fosamax)
- Risedronate (Actonel)
- Zoledronic acid (Reclast)
- Ibandronate (Boniva)
Bisphosphonates: Mechanism of action
Bisphosphonates a Half life: 1. In plasma? 2. In bone?
Inhibit bone resorption by decreasing the number and function of osteoclasts
Half Life
- In plasma: 1 hour
- In bone: may persist for a lifetime
Bisphosphonates: Pharmacokinetics
- Absorption?
- Cleared?
- Remaining amount taken up by?
- Only 1-5% of the oral dose is absorbed
- 70% of the absorbed dose is then cleared renally
- The remaining 30% is taken up by the bone
Bisphosphonates: pretreatment screening and testing
6
- GFR needs to be > 30-35 ml/min
- Correct calcium and vitamin D deficiencies prior to administration
25 OH Vit D levels should be > 25-30 ng/ml (62-75 nmol/L) - Review history and symptoms for any abnormalities of the esophagus (stricture or achalasia) or delayed gastric emptying
- Ability to remain upright for 30-60 min post oral dose
- Recent fracture (wait 4-6 weeks to start rx)
- Plans for dental extractions or implants?
- May increase risk for osteonecrosis of the jaw
Oral bisphosphonates: contraindications
4
- Barrett’s esophagus
- Active upper GI disease
- DC if symptoms of esophagitis occurs
- If GFR is not greater then 30-35 ml/min
Aldronate (Fosamax)
- Advanatges? 3
- Take how often?
- Generic, low cost
- Greater increase in BMD then Actonel at all sites after 12 months of therapy
- Well tolerated and effective for 5-10 y
No difference in incidence of 2
-Daily or weekly
Risedronate (Actonel)
- Advantage? 2
- How often?
- May have less GI side effects
- Well tolerated and effective for up to 7 y
Daily, weekly or monthly
What are the IV therapy biphophanates? 2
When would you use these? 2
- Zoledronic Acid 5mg/year
(Reclast) - Ibandronate (Boniva)
- If cannot tolerate oral therapy or if failure to respond to oral therapy
- No evidence that it decreases hip fracture
Bisphosphonates: Side effects
- GI
- Hypocalcemia (more common with IV)
- Musculoskeletal pain
- Ocular
- Atypical fracture
- Osteonecrosis of the jaw
- Flu-like symptoms post IV infusion
Bisphosphonates: Side effects
GI? 3 (possibly 4)
- Reflux,
- esophagitis,
- ulcers
- Esophageal cancer(?)
Biphosphanates Ocular SE?
5
What kind of atypical fxs? 2
- Eye pain,
- blurred vision,
- conjunctivitis,
- uveitis,
- scleritis
- Subtrochanteric
- Lateral
Bisphosphonates side effects: Osteonecrosis of the jaw
Risk Factors?
8
- IV bisphosphonates
- Anticancer therapy
- Dental extractions
- Dental implants
- Poorly fitting dentures
- Glucocorticoids
- Smoking
- Pre-existing dental disease
Bisphosphonates:
Duration of therapy
1. Aldronate (Fosamax) and Risedronate (Actonel)
-When do you reassess need?
- When would you d/c therapy?
- When would you continue it?
- 5 years
- Low risk, no fractures, T score > -2.5 may consider discontinuation of therapy
- High risk, T score ≤ -3.5 continue therapy for up to 10 years
Estrogen agonist/antagonist (SERMs): Raloxifene (Evista)
1. Indicated for?
- Less effective then?
- Indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis
- Less effective than estrogen and bisphosphonates
Raloxifene (Evista)
- Dose?
- SE? 3
60mg once daily
Side effects:
- DVT,
- hot flashes,
- endometrial cancer