Disorders of Bone Flashcards
Osteoporosis is:
*The most common metabolic bone disease in the US
* Is a chronic and progressive disease
* Becomes clinically apparent once a fracture occurs
Osteoporosis
The imbalance of new bone formation and old bone resorption. For some they may not make enough new bone, for others have too
much reabsorption of old bone, and for others both may occur
Osteopenia
A condition of low bone density with a T-score below normal range from -1.0 to -2.5
Normal bone is defined by a T-score higher than -1.0
Osteoporosis T score & FRAX score
T-score of -2.5 or below in the spine, femoral neck, or total hip
Any fragility fracture
Osteopenia + FRAX score > 3% risk of hip fracture or > 20% risk of major osteoporotic
fracture
Severe Osteoporosis T-score -2.5 with fragility fracture or T-score -3.0
or greater
Who gets osteoporosis?
- Postmenopausal women – most common
- Men – over 65 or secondary cause
- Premenopausal women – usually a secondary cause
Pathogenesis of Osteoporosis
Menopause
Cellular Senescence of osteoblasts and osteoclasts
Changes to Gut Microbiome
Sex steroid deficiency
Clinical Manifestations of Osteoporosis
No clinical manifestations until a fracture is present
Pain? – many with hip or feet pain assume they have osteoporosis, but
osteoporosis is painless until a fracture occurs
Osteomalacia causes bone pain
Common Fractures of Osteoporosis
Vertebral are the most common, 2/3 are asymptomatic
Hip Fracture affects up to 15% of women or 5% of men by age 80
Risk of hip fracture increases exponentially with age
Colles fracture (distal radius) most common after menopause
Diagnosis of Osteoporosis
Usually occurs in the presence of a fragility fracture
Fragility fractures occur from a fall at a standing height or less, without major trauma
Fragility fractures of the spine can occur spontaneously with minimal or no trauma
Fracture of the skull, cervical spine, hands, feet, and ankles are not associated with
fragility fractures
Stress fractures are not fragility fractures since these are due to repetitive injury
The WHO states that _____ is the standard test to diagnose osteoporosis in the absence of a fragility fracture.
BMD assessment by DXA
Dexa Scan
DXA gives an accurate and precise estimate of bone mineral density
Usually provides measurements of the spine and hips since these sites have
the greatest impact on patient’s health.
BMD has the highest predictive value for hip fracture
If pharmacologic therapy is initiated – BMD of the spine detects earlier
responses to therapy than hip BMD
T-score is the standard deviation difference between the bone mineral density
of a patient and a ______
young-adult reference population.
A T-score of_____ mean is
defined as osteoporosis.
2.5 standard deviation or more below the young-adult
A T-score of _____ mean is defined
as osteopenia.
1 to 2.4 stand deviation below the young-adult
Z-score is the comparison of _____
a patient’s bone mineral density with that of an age-matched population.
A Z-score of _____ should alert one to other coexisting problems that
can contribute to osteoporosis.
less than 2
coexisting problems that
can contribute to osteoporosis
Glucocorticoid therapy
Alcoholism
Hyperparathyroidism
Cushing’s Syndrome
Celiac Disease
Renal or Liver Disease
When to Screen for Osteoporosis
All women aged 65 or older should be screened
Postmenopausal women younger than age 65 with clinical risk factors should
be screened
Males >70 or 50-69 with osteoporosis risk factors
Risk Factors for osteoporosis
Low body weight, history of hip fracture/fragility fracture, tobacco use, glucocorticoid therapy, excessive alcohol intake, rheumatoid arthritis, chronic liver disease, inflammatory bowel disease
Laboratory Testing for Osteoporosis
Vitamin D, CBC, and BMP
Other tests if secondary causes are a concern:
TSH, PTH, Celiac panel, 24-hour urine for calcium, Cr measurement, urinary cortisol
Treatment for Osteoporosis
Oral Bisphosphonates are initial therapy of choice. Bisphosphonates inhibit resorption of bone by osteoclasts. They may have an effect on osteoblasts as well.
For postmenopausal women with osteoporosis (T-score < -2.5) or with a
history of a fragility fracture.
High-risk postmenopausal women with T-score between -1.0 to -2.5
Risk fracture is determined based on Fracture Risk assessment Tool (FRAX)
FRAX score
Gives the 10-year probability of developing a hip fracture or other major
osteoporotic fractures given BMD of the femoral neck and assessing for other
clinic risk factors for fracture.
High risk is 10-year probability of > 3% of hip fracture and >20% for major
osteoporotic fracture.
Bisphosphonates
Fosamax – alendronate, 70 mg weekly
Actonel – risedronate, 35 mg weekly or 150 mg monthly
Take on an empty stomach and remain upright for 30 to 60 minutes
Reclast – zoledronic acid, 5 mg once a year (tx), 5 mg every two years (prevention)
For those who cannot tolerate oral form or have impaired renal function
Bisphosphonates contraindications
Esophageal disorders (oral formulation)
Inability to follow dosing requirements
Chronic kidney disease, GFR <30
Bariatric Surgery – Roux-en-Y gastric bypass (oral formulation)
Bisphosphanate side effects
Bone pain
Digestive problems
Flu-like symptoms
Low calcium levels
Change in kidney function
Rash
Osteonecrosis
RANKL Inhibitors MOA and indication
Prevent the development of osteoclasts. Preventing osteoclasts from breaking
down bone.
This is both a first line and second line agent in the treatment of Osteoporosis.
Used for those who are intolerant of both oral and IV bisphosphonates or
those with severe osteoporosis, T-score -3.5 or lower even in the absence of
fracture.
RANKL Inhibitors
Prolia – denosumab, 60 mg SQ every 6 months
RANKL Inhibitors contraindications
hypocalcemia
RANKL Inhibitors side effecs
Hypocalcemia
Osteonecrosis
Bone fractures
Rash
Bone, joint, or muscle pain
Infections of the bladder, skin, or ear
Endocarditis
Hormone Treatment for Osteoporosis
Estrogen is no longer considered a treatment due to risk factors of breast
cancer
Evista – raloxifene a Selective estrogen receptor modulator.
Forteo – teriparatide a recombinant parathyroid hormone
Tymlos – abaloparatide a synthetic analog of human parathyroid
hormone-related peptide
Raloxifene
Primarily used for management of breast cancer. May be used for prevention
of osteoporosis. Inhibits bone resorption. Has shown greatest effects with
prevention of vertebral fractures, not so much with non-vertebral fractures.
Forteo/Tymlos
Parathyroid hormone causes the body to form new bone and increase the
strength and density of existing bone. This medication actually stimulates
bone formation.
Forte/Tymlos side effects
Usually associated with hypercalciuria
Pain
Weakness
Dizziness/Vertigo
Depression
Difficulty breathing
Nausea, vomiting, and constipation
Abdominal Pain
Romosozumab name and MOA
Brand Name Evenity
Recently approved monoclonal antibody that inhibits sclerostin, increasing bone formation
and decreasing bone resorption
International Society for Clinical Densitometry (ISCD) recommends retesting with
_____ after initiation of therapy
Dexa 1 to 2 years
Bisphosphonates
Alendronate 15 (Vertebral) 91 (Hip)
Risendronate 20 (vertebral) 91 (Hip)
Zoledronic Acid 14 (vertebral) 91 (Hip)
Osteonecrosis
A pathologic process that is associated with numerous etiologies and
treatments. When there has been obvious damage to bone vasculature or
injury to the bone or marrow, it is easy to identify a cause for the necrosis.
However, many patients suffer bone necrosis with no known mechanism for
the cause. The process is progressive and leads to joint destruction in months
to two years in most individuals.
Osteonecrosis types
Avascular necrosis
Aseptic necrosis
Atraumatic necrosis
Ischemic necrosis
Etiology of Osteonecrosis
Traumatic: Fracture, Dislocation, Minor trauma to the bone
Nontraumatic causes:
Corticosteroid use
Alcohol consumption
SLE
Chronic renal failure or hemodialysis
Pancreatitis
Pregnancy
Tobacco Use
HIV
Hyperuricemia
Pathogenesis of Osteonecrosis
Most believe it is due to combined effects:
Genetic predisposition
Metabolic factors
Vascular damage
Increased intraosseous pressure
Mechanical stressors
Clinical Manifestation of Osteonecrosis
Usually occurs in the femoral head
When other joints are involved, shoulder or knee, the hip should also be
evaluated.
Early detection is key to joint collapse and need for replacement
High index of suspicion for those patients on chronic corticosteroid use
Pain is the most common symptom
Groin pain
Pain upon weight-bearing or motion induced pain
Pain at rest (about 2/3) pain at night (1/3)
Two main types of osteonecrosis
Idiopathic – Legg-Calve-Perthes Disease
Slipped capital femoral epiphysis – usually occurs in adolescents
Diagnostic Evaluation of Osteonecrosis
Physical findings are usually nonspecific
Begin with plain radiograph of the hip. Anterior-posterior and frog leg lateral
views.
Usual findings are:
Crescent sign (pathognomonic) – evidence of subchondral collapse
Later joint space narrowing and degenerative changes of the acetabulum are visible
_____ is the gold standard to diagnosis Osteonecrosis.
MRI without contrast agent
Three approaches to therapy for osteonecrosis
Ultimate goal is to preserve the native joint
Non-operative management
Joint-preserving procedures
Joint Replacement
Staging of Osteonecrosis
Stage 0 – All diagnostic studies normal and diagnosis by histology only.
Stage 1 – Plain radiographs and CT normal, scintigraph or MRI positive, and biopsy positive
Stage 2 – Radiographs positive but no collapse (no crescent sign)
Early Stage 3 – Crescent sign on the radiograph and/or flattening of articular surface of the
femoral head. No collapse.
Late Stage 3 – Collapse on the radiograph and/or flattening of articular surface of the femoral head.
Stage 4 – Joint space narrowing on plain radiography and acetabular involvement
Non-operative Management of Osteonecrosis
Has been shown to be ineffective at stopping the progression of the disease
when located in the hip or shoulder
Includes:
Bed rest
Partial weight-bearing with crutches
Analgesics
Pharmacologic agents
Pharmacologic Agents for osteonecrosis
Bisphosphonates
Statins – thought to reduce differentiation for marrow cells to fat cells
Anticoagulants – when due to thrombophilia
Electrical Stimulation
Joint Preserving Procedures for osteonecrosis
Core Decompression
Osteotomy
Both have similar efficacy in early disease. But, osteotomy is better when there is collapse of the femoral head on initial diagnosis.
Paget’s Disease
Also known as osteitis deformans. A focal disorder of bone metabolism
resulting in an accelerated rate of bone remodeling and overgrowth of bone.
May occur at a single site or multiple sites.
Usually affects the skull, spine, pelvis, and long bones of the lower
extremities
A disease of the osteoclast
Pagets disease is a disease of the _____
osteoclast
Pathogenesis of Paget’s Disease of Bone
A disease of the osteoclast
The osteoclast has an unusual appearance with too many nucleoli
Osteoclasts show hypersensitivity to vitamin D
Inheritance of Paget’s disease
The possibility of viral involvement in Paget’s disease continues to be investigated
Clinical Manifestations of Paget’s Disease
Patients are usually asymptomatic
Symptoms occur due to overgrowth or deformity of the bone
Pain may be due to pagetic lesion, arthritis, nerve impingement, or tumor
The two main symptoms are pain and deformity
The pain is often described as a mild to moderate deep ache that persists
throughout the day and at rest. Some have pain at night as well.
Clinical Manifestations of Paget’s Disease within the skull
Hearing loss, headaches, dizziness, jaw deformity or malocclusion
Clinical Manifestations of Paget’s Disease within the spine and pelvis
Spinal stenosis, nerve compression, compression fracture
Clinical Manifestations of Paget’s Disease in long bones
Bowing deformities and increased risk for fracture
Tumors
Primarily osteosarcoma
Diagnosis of Paget’s Disease
Often found incidentally on lab or radiographs performed for other reasons
Elevated alkaline phosphatase
Normal calcium and phosphorus levels
X-ray will show osteolytic lesions, bone thickening, and enlarged bones
X-ray is the predominant diagnostic factor.
Bone Scintigraphy reveals increased uptake activity at focally active pagetic
sites
Goal of treatment pagets disease
Ease pain
Decrease rate of bone remodeling towards normal
Slow disease progression
Indications for Treatment for Paget’s Disease
Symptomatic patients
Asymptomatic patients with one of the following:
Biochemically active disease with increased Alkaline Phosphatase
Alkaline phosphatase 2 to 4 times normal
Normal alkaline phosphatase with abnormal bone scintigraphy at a site where complications
can occur
Planned surgery at an active pagetic site
_____ are the drug of choice to treat Paget’s disease.
Bisphosphonates
