Metabolic Bone Diseases Flashcards
Metabolic Bone Diseases
Osteoporosis Paget's disease Osteomalacia Rickets Renal osteodystrophy
Pathophysiology of Osteoporosis
Bone resorption outpaces bone deposition
Negative Feedback Loop for Bone Remodeling
Hormonal process that maintains calcium homeostasis
Types of Stress on the Skeleton
Mechanical
Gravitational
What is osteoclast activity stimulated by?
PTH Calcitonin (low levels) GF IL-6 Lack of gonadal hormones
Osteoblasts
Builders of bone matrix
Decreased number with aging
How can the thyroid gland stimulate or inhibit osteoclast activity?
Hyperthyroidism: stimulate osteoclast activity
Increased plasma calcium: release of calcitonin
Risk Factors for Osteoporosis
Age (>50) Gender Race (white, Asian) Activity level Diet Hormonal Meds: gonadal hormones Family history Medical history
Components of Diet in Osteoporososis
ETOH
Tobacco
Low calcium intake or altered ability to absorb
Hormonal Aspects with Osteoporosis
Amenorrhea Late menarche Early menopause Post menopausal state Low testosterone Low estrogen
Medical Conditions Associated with Osteoporosis
Rheumatologic conditions Malabsorption syndromes Hypogonadism Hyperthyroidism Chronic kidney disease Chronic liver disease COPD Neurologic disorders (unable to ambulate or exercise) DM
Medications that can Decrease Bone Density
Heparin Warfarin (+/-) Cyclosporine Medroxyprogesterone acetate (Provera) Vitamin A Loop diuretics Chemo drugs Antiseizure meds PPIs H2 blockers Antidepressants (TCA's & SSRI's) Glucocorticoids
Prevention of Osteoporosis
Exercise Appropriate vitamin D and calcium intake Cessation of tobacco use ETOH in moderation Screening tests
What is the standard test for the evaluation of bone mineral density?
DEXA scan
Indications for a DEXA Scan
Currently 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 Scan Screening Guidelines
Women >65
Men >70
Younger postmenopausal women and men with risk factors
Adults with fragility fractures
Condition associated with low bone mass
Medications associated with low bone mass
Define T-Score
Bone mineral density compared to what is normally expected in a young healthy adult based on gender
What T-score indicates osteoporosis?
Less than 2.5
In what populations is a Z-score used instead of a T-score?
Premenopausal women Men younger than 50 Children African Americans Native Americans
What is quantitative calcaneal ultrasonography effective at predicting?
Femoral neck, hip, & spine fractures
Pros of Quantitative Calcaneal Ultrasonography
Lower cost than DEXA scan
Portable
No radiation exposure
Screening test NOT diagnosis
Indications for Vertebral Imaging for Osteoporosis Screening
Bone testing not available in women >70 and men >80
T-scores of -1.5 in women 65-69 and men 75-79
Women 50-64 and men 50-69 with risk factors
Low trauma fracture
Historical height loss of 1.5”+
Prospective height loss of 0.8”+
Recent/ongoing long term glucocorticoid treatment
After initial vertebral imaging, when should you reemerge to evaluate?
Loss of height
Suspect new vertebral fracture
New back pain
Postural change
Work Up of Osteoporosis
H&P
Labs
+/- x-rays
DEXA scan
History in the Workup of Osteoporosis
Any history of disease
Family history
History of low vitamin D, prior bone density testing, or prior fractures
Medication review
Signs and Symptoms of Osteoporosis
Asymptomatic unless fracture
Gradual loss of height
Dowager’s hump
Possible Labs to Diagnose Osteoporosis (Depends on comorbidities & history)
CBC CMP Serum magnesium TSH 25-OH vitamin D PTH Testosterone (younger men) 24 H urine calcium
Indications for X-ray to Look for Osteopenia
Symptomatic patients
Asymptomatic patients if vertebral fracture suspected
Non-Pharmacologic Treatment of Osteoporosis
Calcium
Vitamin D
Exercise
SE of Calcium
Nephrolithiasis
Dyspepsia
Constipation
Interfere with absorption of iron and thyroid hormone
Calcium Citrate vs. Calcium Carbonate
Citrate better with H2 blockers and PPIs
Citrate less likely to cause nephrolithiasis
Citrate harder to take
SE of Excessive Vitamin D Levels
Hypercalcemia
Hypercalciuria
Kidney stones
Guidelines for Pharmacologic Treatment of Osteoporosis
Age 50 and older + hip or vertebral fracture OR T-scores less than -2.5
T-score -1 to -2.5 in postmenopausal women and men 50 and older + 10 year hip fracture possibility >3% OR 10 year major fracture probability of >20%
Pharmacologic Options for Treatment of Osteoporosis
Bisphosphonates Calcitonin Estrogen agonist/antagonist Hormone therapy PTH 1-34 RANKL inhibitor Tissue selective estrogen complex
Oral Bisphosphonates
Alendronate (Fosamax)
Risedronate (Actonel)
IV Bisphosphonates
Zoledronic acid (Reclast) Ibandronate (Boniva)
MOA of Bisphosphonates
Inhibit bone resorption by decreasing number and function of osteoclasts
What portion of oral bisphosphonates are taken up by the bone?
1-5% absorbed
30% of absorbed taken up by bones
Bisphosphonates Pre-treatment Screening and Testing
GFR >30-35 mL/min
Correct calcium and vitamin D deficiencies prior to administration
Review history for symptoms of abnormalities of esophagus or delayed gastric emptying
Ability to be upright for 30-60 minutes post oral dose
Recent fracture (wait)
Plans for dental extractions
Contraindications for Oral Bisphosphonates
Barrett’s esophagus
Active upper Gi disease
D/C if symptoms of esophagitis occur
GFR less than 30-35 mL/min
Aldronate (Fosamax)
Generic Low cost Greater increase in BMD than Actonel Well tolerated Effective for 5-10 years Daily or weekly
Risedronate (Actonel)
Less GI side effects
Well tolerated
Effective for up to 7 years
Daily, weekly, or monthly
Zoledronic Acid (Reclast)
Cannot tolerate oral therapy
Failure to respond to oral therapy
15 min IV infusion once a year
Ibandronate (Boniva)
No evidence of decreased hip fracture
Q 3 months
SE of Bisphosphantates
Reflux Esophagitis Ulcers Hypocalcemia Musculoskeletal pain (large muscle groups) Eye pain Blurred vision Conjunctivitis Uveitis Scleritis Atypical fractures: subtrochanteric or lateral Osteonecrosis of jaw Flu-like symptoms post infusion
Risk Factors for Osteonecrosis of the Jaw
IV bisphosphonates Anti-cancer therapy Dental extractions Dental implants Poorly fitting dentures Glucocorticoids Smoking Pre-existing dental disease
Duration of Oral Bisphosphonate Therapy
Reassess at 5 years
T-score >-2.5 discontinue
T-score less than -3.5 continue up to 10 years
Raloxifene (Evista): estrogen agonist/antagonist
Decrease risk of vertebral fracture by 30% with prior history of fracture
Decrease risk of vertebral fracture by 55% with no history of previous fracture
Less effective than estrogen and bisphosphonates
Indications for Raloxifene (Evista)
Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis
SE of Raloxifene (Evista)
DVT
Hot flashes
Endometrial cancer
Indications for Calcitonin
Osteoporosis in women >5 years post menopause
Calcitonin and Vertebral Fractures
Reduction by about 30% in persons with previous fractures
Contraindications of Calcitonin
History of allergy to salmon
SE of Calcitonin
Rhinitis
Epistaxis
Allergic reactions
Example of Hormone Replacement Therapy
Prempro (estrogen/progesterone)
Prempro and Osteoporosis
5 years duration
Decrease vertebral and hip fractures by 34%
Decrease other osteoporotic fractures by 23%
SE of Hormone Replacement Therapy
Increased risks of MI, CVA, invasive breast cancer, PE, DVT during treatment
No MI risk if within 10 years post menopause
MOA of Teriparatide (Forteo)
Stimulates bone formation
Indications for Teriparatide (Forteo)
Severe osteoporosis when other treatments have failed
Effects of Teriparatide (Forteo)
Decrease risk of vertebral fracture by 65%
Decrease non-vertebral fracture by 53%
Administration and Duration of Teriparatide (Forteo)
A: subQ injection daily
D: 24 months max
SE of Teriparatide (Forteo)
Leg cramps
Nausea
Dizziness
Increased incidence of osteosarcoma (animal studies)
Contraindications of Teriparatide (Forteo)
At risk for osteosarcoma Paget's disease Prior RT of skeleton Bone mets Hypercalcemia Hx of skeletal malignancy
MOA of Denosumab (Prolia)
Decreases bone absorption by inhibiting osteoclast activity
Indications for Denosumab (Prolia)
Postmenopausal women and men at high risk for fracture
Cancer patients
Follow Up on Pharmacologic Therapy for Osteoporosis
Monitor for SE
Monitor for recurrent fractures
Yearly height management
Serial DEXA scans (every 2 years)
Treatment of Osteoporosis for Special Populations
Glucocorticoid induced
Renal failure (calcitriol)
Androgen deficiency (testosterone)
Malabsorption
What part of the body does Paget’s Disease (Osteitis deformans) commonly involve?
Axial skeleton Skull Thoracolumbar spine Pelvis Long bones of the lower extremity
Pathophysiology of Paget’s Disease
Increased rate of bone remodeling
Overgrowth of bone at a single or multiple sites
Impaired integrity of affected bone
Epidemiology of Paget’s Disease
Genetic disorder Etiology: possibly viral Age: 55+ Men > women Associated with osteosarcoma
Symptoms of Paget’s Disease
Arthritis Pain Bone deformity Fractures Radiculopathy Chronic back pain Impaired functional status Hearing loss Headache Vertigo Tinnitus Asyptomatic
Labs for Paget’s Disease
Increased serum alkaline phosphatase
Normal calcium
Normal phosphorus
Imaging for Paget’s Disease
X-ray
Bone scan
Findings on X-rays for Paget’s Disease
Mixed lytic and sclerotic lesions
Long bone bowing
Bone thickening and enlargement
Findings on Bone Scans for Paget’s Disease
Increased bone remodeling and blood flow
Diagnosing Paget’s Disease
H&P X-rays Elevated alkaline phosphatase Baseline bone scan Baseline calcium, 25-OH vitamin D, phosphorus
Goals of Treatment of Paget’s Disease
Decrease pain
Slow bone remodeling
Treatment of Paget’s Disease
Supportive: calcium, vitamin D
Bisphosphonates
Define Osteomalacia
Decreased mineralization of newly formed bone (soft bones)
Causes of Osteomalacia
Disorders that result in hypocalcemia, hypophosphatemia, or direct inhibition of the mineralization process
2 Main Causes of Osteomalacia
Insufficient calcium absorption from the intestine
Phosphate deficiency
Etiology of Osteomalacia
Malabsorption Gastric bypass surgery Celiac sprue: malabsorption of vitamin D Chronic hepatic disease: vitamin D stored in liver Chronic kidney disease
Symptoms of Osteomalacia
Asymptomatic Bone pain and muscle weakness Bone tenderness Fracture Difficulty walking and waddling gait Muscle spasms, cramps Positive Chvostek's sign Tingling/numbness Inability to ambulate
Positive Chvostek’s Sign
Twitching of the facial muscles in response to tapping over the area of the facial nerve
Work Up for Osteomalacia
Calcium Phosphate Alkaline phosphatase 25-OH vitamin D PTH Electrolytes BUN and creatinine Possible biopsy
Nutritional Deficiency and Osteomalacia Labs
Increased alkaline phosphatase Decreased serum calcium and phosphorus Decreased urinary calcium Decreased 25-OH vitamin D Increased PTH
X-ray Findings for Osteomalacia
Reduced bone density with thinning of the cortex
Looser pseudofractures
Fissures
Loss of radiologic distinctness of vertebral body trabecular and concavity of the vertebral bodies
Define Looser’s Pseudofractures
Cortical infarctions
Wide transverse lucencies traversing bone usually at right angles to involved cortex
Treatment of Osteomalacia
Correction of underlying cause
Vitamin D supplementation
Most Common Fractures in Osteomalacia
Distal radius
Proximal femur
What vitamin D supplement is used in renal and hepatic disease to treat osteomalacia?
Calcitriol
Define Rickets
Deficient mineralization at the growth plate
Prior to closure of the growth plates
Osteomalacia after closure of growth plates
Cause of Rickets
Decreased calcium
Decreased vitamin D
Renal phophate wasting
Define Renal Osteodystrophy
Bone disease secondary to chronic kidney failure
Types of Bone Disease Secondary to Renal Osteodystrophy
Osteitis fibrosa
Mixed uremic osteodystrophy
Osteomalacia
Adynamic bone
Effects of Renal Osteodystrophy
Calcium, phosphorus, vitmain D metabolism
PTH
Bone turnover
Bone mineralization, volume, linear growth
Bone strength
Extraskeletal calcification
Major Contributor to Renal Osteodystrophy
Secondary hyperparathyroidism
Secondary Hyperparathyroidism in Chronic Kidney Disease
GFR below 60 mL/min Calcitriol deficiency Hyperphosphatemia Hypocalcemia Increase in PTH
Pathophysiology of Osteitis Fibrosis
High turnover secondary to hyperparathyroidism
Pathophysiology of Dynamic Bone Disease
Low turnover due to suppression of the parathyroid glands
Most common CKD related bone disease
Pathophysiology of Osteomalacia
Low turnover with abnormal mineralization
Pathophysiology of Mixed Uremic Osteodystrophy
Either high or low turnover and abnormal mineralization
Treatment of Parathyroidism in CKD
Dietary restriction of phosphorus
Supplemental active form of vitamin D
Phosphate binders
