Metabolic Bone Disease Flashcards
Osteoporosis definition
- a condition characterized by decreased bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and suscepti-bility to fracture bone mineral density (BMD) ≥2.5 standard deviations below the peak bone mass for young adults (i.e. T-score ≤–2.5)
- osteopenia: BMD with T-score between –1.0 and –2.5
Osteoporosis etiology and pathophysiology
Primary Osteoporosis (95% of osteoporosis in women and 80% in men) • primary type 1: most common in post-menopausal women, due to decline in estrogen, worsens with age • primary type 2: occurs after age 75, seen in females and males at 2:1 ratio, possibly due to zinc deficiency
Secondary Osteoporosis
- gastrointestinal diseases ■ gastrectomy ■ malabsorption (e.g. celiac disease) ■ chronic liver disease
- bone marrow disorders ■ multiple myeloma ■ lymphoma ■ leukemia
- endocrinopathies ■ Cushing’s syndrome ■ hyperparathyroidism ■ hyperthyroidism ■ premature menopause ■ DM ■ hypogonadism
- malignancy ■ secondary to chemotherapy ■ myeloma
- drugs ■ corticosteroid therapy ■ phenytoin ■ chronic heparin therapy ■ androgen deprivation therapy ■ aromatase inhibitors
- other ■ rheumatologic disorders ◆ rheumatoid arthritis ◆ SLE ◆ ankylosing spondylitis ■ renal disease ■ poor nutrition ■ immobilization
- COPD (due to disease, tobacco, and glucocorticoid use)
Osteoporosis clinical features
- commonly asymptomatic
- height loss due to collapsed vertebrae
• fractures: most commonly in hip, vertebrae, humerus, and wrist
■ fragility fractures: fracture with fall from standing heght
■ Dowager’s hump: collapse fracture of vertebral bodies in mid-dorsal region
■ x-ray: vertebral compression and crush fractures, wedge fractures, “codfishing” sign (weakening of subchondral plates and expansion of intervertebral discs)
• pain, especially backache, associated with fractures
Osteoporosis approach
- assess risk factors for osteoporosis on history and physical
- decide if patient requires BMD testing with dual-energy x-ray absorptiometry (DEXA): men and women ≥65 yr or younger if presence of risk factors
- initial investigations
■ all patients with osteoporosis: calcium corrected for albumin, CBC, creatinine, ALP, TSH
■ also consider serum and urine protein electrophoresis, celiac workup, and 24 h urinary Ca2+ excretion to rule out additional secondary causes
■ 25-OH-Vitamin D level should only be measured after 3-4 mo of adequate supplementation and should not be repeated if an optimal level ≥75 nmol/L is achieved
■ lateral thoracic and lumbar x-ray if clinical evidence of vertebral fracture - assess 10-yr fracture risk by combining BMD result and risk factors (only if ≥50 yr)
1) WHO Fracture Risk Assessment Tool (FRAX)
2) Canadian Association of Radiologists and Osteoporosis Canada Risk Assessment Tool (CAROC)
◆ approach to management guided by 10-yr risk stratification into low, medium, high risk - for all patients being assessed for osteoporosis, encourage appropriate lifestyle changes
Indications for BMD testing
Older adults (age 50+ years):
All women and men age ≥65 yr
Menopausal women, and men aged 50-64 yr with clinical risk factors for fracture:
Fragility fracture after age 40
Prolonged glucocorticoid use
Other high-risk medication use (aromatase inhibitors, androgen deprivation therapy)
Parental hip fracture
Vertebral fracture or osteopenia identified on x-ray
Current smoking
High alcohol intake
Low body weight (<60 kg) or major weight loss (>10% of weight at age 25 yr)
Rheumatoid arthritis
Other disorders strongly associated with osteoporosis: primary hyperparathyroidism, type 1 DM, osteogenesis imperfecta, uncontrolled hyperthyroidism, hypogonadism or premature menopause (<45 yr), Cushing’s disease, chronic malnutrition or malabsorption, chronic liver disease, COPD and chronic inflammatory conditions (e.g. inflammatory bowel disease)
Younger adults (age <50 years): Fragility fracture: Prolonged use of glucocorticoids Use of other high-risk medications (aromatase inhibitors, androgen deprivation therapy, anticonvulsants) Hypogonadism or premature menopause Malabsorption syndrome Primary hyperparathyroidism Other disorders strongly associated with rapid bone loss and/or fracture
Osteoporosis risk stratification and next steps
Low Risk - 10 yr fracture risk <10%
Unlikely to benefit from pharmacotherapy; encourage lifestyle changes
Reassess risk in 5 yr
Medium Risk - 10 yr fracture risk 10-20%
Discuss patient preference for management and consider additional risk factors Factors that warrant consideration for pharmacological therapy:
Additional vertebral fracture(s) identified on vertebral fracture assessment (VFA) or lateral spine x-ray
Previous wrist fracture in individuals ≥65 or with T-score ≤–2.5
Lumbar spine T-score much lower than femoral neck T-score
Rapid bone loss
Men receiving androgen-deprivation therapy for prostate cancer
Women receiving aromatase-inhibitor therapy for breast cancer
Long-term or repeated systemic glucocorticoid use (oral or parenteral) that does not meet the conventional criteria for recent prolonged systemic glucocorticoid use
Recurrent falls (defined as falling 2 or more times in the past 12 mo)
Other disorders strongly associated with osteoporosis
Repeat BMD and reassess risk every 1-3 yr initially
High Risk - 10 yr fracture risk >20%; OR Prior fragility fracture of hip or spine; OR More than one fragility fracture
Start pharmacotherapy
Osteoporosis treatment
Treatment for both men and women
Lifestyle
Diet: Elemental calcium 1000-1200 mg/d; Vit D 1000 IU/d
Exercise: 3x30 min weight-bearing exercises/wk
Cessation of smoking, reduce caffeine intake
Stop/avoid osteoporosis-inducing medications
Drug therapy:
Bisphosphonate: inhibitors of osteoclast binding
1st line in prevention of hip, nonvertebral, and vertebral # (Grade A): alendronate, risedronate, zoledronic acid
2nd line (Grade B): etidronate
RANKL Inhibitors
Denosumab: 1st line in prevention of hip, nonvertebral, vertebral # (Grade A)
Parathyroid Hormone
YES fragility #: 18-24 mo duration
Calcitonin (2nd line) osteoclast receptor binding
YES fragility #: Calcitonin 200 IU nasally OD with Calcitriol 0.25 µg bid
Treatment specific to post-menopausal women:
SERM (selective estrogenreceptor modulator): agonistic effect on bone but antagonistic effect on uterus and breast
Raloxifene: 1st line in prevention of verteb al # (Grade A)
+ve: prevents osteoporotic # (Gr de A to B evidence), improves lipid profile, decreased breast ca risk
-ve: increased risk of DVT/PE, stroke mortality, hot flashes, leg cramps
HRT: combined estrogen + progesterone
1st line in prevention of hip, nonvertebral, and vertebral # (Grade A)
For most women, risks > benefits
Combined estrogen/progestin prevents hip, vertebral, total #
Increased risks of breast cancer, cardiovascular events, and DVT/PE
Clinical signs of fractures or osteoporosis
- Height loss >3 cm (Sn 92%)
- Weight <51 kg
- Kyphosis (Sp 92%)
- Tooth count <20 (Sp 92%)
- Grip strength
- Armspan-height difference >5 cm (Sp 76%)
- Wall-occiput distance >0 cm (Sp 87%)
- Rib-pelvis distance ≤2 finger breadth (Sn 88%)
Calcium Plus Vitamin D Supplementation and Risk of Fractures. Osteoporosis
Systematic analysis suggests that Vitamin D and Calcium therapy significantly decreases fracture risk. This study did not specifically look at individuals with osteoporosis. However, it still supports that Vitamin D and Calcium should continue to be used as preventative treatment for individuals at increased risk of fractures.
Calcium Plus Vitamin D Supplementation and Risk of Fractures. Osteoporosis
Systematic analysis suggests that Vitamin D and Calcium therapy significantly decreases fracture risk. This study did not specifically look at individuals with osteoporosis. However, it still supports that Vitamin D and Calcium should continue to be used as preventative treatment for individuals at increased risk of fractures.
What is considered a positive wall-occiput test for thoracic fracture
> 0 cm
What is considered a positive Rib-Pelvis distance test for Lumbar fracture
Rib-pelvis distance 0-2 fringerbreadths
What to ask before prescribing Calcitonin
Before prescribing Calcitonin, remember to ask about fish allergies
Rickets definition
osteopenia with disordered calcification leading to a higher proportion of osteoid (unmineralized) tissue prior to epiphyseal closure (in childhood)
Osteomalacia definition
osteopenia with disordered calcification leading to a higher proportion of osteoid (unmineralized) tissue after epiphyseal closure (in adulthood)
