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Introduction

Definition (main characteristics common to both osteopenia and osteoporosis)

age-related decrease in bone mass secondary to uncoupling of osteoclast-osteoblast
activity
disrupted microarchitecture
WHO definition (see table below)
Epidemiology
incidence
10 million Americans and 200 million people worldwide have osteoporosis
34 million Americans have osteopenia
1.5 million osteoporotic fractures occur each year
700,000 are vertebral fractures
300,000 are hip fractures
200,000 are wrist fractures
demographics
male: female ratio is 1:4
men have a higher prevalence of secondary osteoporosis (60%) including
hypogonadism
glucocorticoid excess
alcoholism
age bracket
osteoporosis
postmenopausal osteoporosis is highest in women aged 50-70 years
senile osteoporosis begins after 70 years
secondary osteoporosis begins at any age
fractures
wrist fractures occur most commonly at age 50-60 years
vertebral fractures occur most commonly at age 60-70 years
hip fractures occur most commonly at age 70-80 years
location of fractures
vertebral body > hip > wrist fractures
risk factors
table of risk factors
Pathophysiology
quantitative, not qualitative, disorder of bone mineralization
factors
failure to build peak bone mass as a young adult
bone loss in later life
Associated conditions
fragility fractures
direct relationship between degree of bone loss and fractures
kyphotic deformity can arise from verteberal body fractures
pelvic ring insufficiency fractures most often treated with bed rest and analgesia
total hip arthroplasty with constrained components are a risk factor for fragility
fractures
Prognosis
prior fragility fracture is the strongest predictor of a future fracture from low energy
trauma
vertebral fractures
associated with 15% increase in 5-year mortality
associated with increased morbidity
back pain
loss of height
poor balance
respiratory compromise
restrictive lung disease
pneumonia
history of 1 vertebral fracture results in 5 fold increased risk of 2nd vertebral
fracture and 5 fold increased risk of hip fracture
history of 2 vertebral fractures is the strongest indicated for further compression
fractures in postmenopausal women
hip fractures
associated with 20% increase in mortality
men have higher mortality rates following hip fractures than women
associated with increased morbidity
reduced quality of life
only one third of patients with hip fractures return to their previous level of
function
history of 1 hip fracture results in up to 10 fold increased risk of 2nd hip fracture
FRAX score
WHO fracture risk assessment tool that calculates the 10-year risk of hip fracture
and 10-year risk of major osteoporosis-related fracture
factors include age, sex, personal history of fracture, low BMI, oral steroid use,
secondary osteoporosis, parental history of hip fracture, smoking status and
alcohol intake.

Classification

Type I (Post menopausal) Type II (Senile)

Age group Post menopausal (highest incidence in 50-70 years old) >70 years old
Bone Trabecular >
Almost exclusively trabecular
affected cortical
Bones
Distal radius and vertebral Hip and pelvis
fractured

Effect on Net negative change in calcium levels because of decreased intestinal absorption Poor calcium
calcium and increased urinary excretion of calcium. absorption

Effect on
Vit D Reduced circulating levels of total (but not free) 1,25 dihydroxyvitamin D. -
Labs

25 hydroxyvitamin D level
low 25 hydroxy cholecalciferol levels (25 hydroxy vit D) in patients sustaining low energy
fractures

Imaging

Radiographs
indications
suspicion of fracture
loss of height
pain in thoracic or lumbar spine
recommended views
lateral spine radiograph
AP pelvis or hip
findings
thinned cortices
loss of trabecular bone
kyphosis
codfish vertebra
sensitivity and specificity
usually not helpful unless > 30% bone loss
Dexa Scan (Dual Energy Xray Absorptiometry)
usually performed in
lumbar spine: measures BMD from L2 to L4 and compiles scores
hip: measure BMD from femoral neck, trochanter, and intertrochanter region and
compiles scores
sensitivity and specificity
most accurate with the least radiation exposure

Term Definition
BMD absolute, patient-specific score determined from certain anatomic areas
T score BMD relative to normal young matched controls (30-year-old women)
Z score BMD relative to similar aged patients

L2-4 lumbar density of 1 to 2.5 standard of deviations (T score -1 to -2.5) below the peak bone
Osteopenia
mass of a 25 year old individual

L2-4 lumbar density > 2.5 standard of deviations (T score <-2.5) below the peak bone mass of
Osteoporosis
a 25 year old individual

Studies

Biopsy
after tetracycline labeling
indications
may be helpful to rule out osteomalacia
Histology
thinned trabeculae
decreased osteon size
enlarged haversian and marrow spaces
osteoclast ruffled border
Increases osteoclast ruffled border seen with
PTH
1,25 dihydroxy Vit D3
Prostaglandin E
flattened ruffled border seen with
Bisphosphonates
Calcitonin

Differential

Osteoporosis Osteomalacia
Reduced bone mass, normal
Definition Bone mass variable, reduced mineralization
mineralization
Post menopausal (Type I) or elderly
Age Any age
(Type II)
Vit D deficiency or abnormal vit D pathway,
Endocrine abnormality, age, idiopathic,
Etiology hypophosphatemia, hypophosphatasia, renal tubular
inactivity, alcohol, calcium deficiency
acidosis

Symptoms
Pain and tenderness at fracture site Generalized bone pain and tenderness
and signs

Appendicular fracture predominance, symmetric,

Xray Axial fracture predominance
includes pseudofractures (Looser zones)
Serum Ca Normal Low or normal
Serum
Normal Low or normal
PO4
ALP Normal Elevated (except hypophosphatasia)
Urinary Ca High or normal Normal or low (high in hypophosphatasia)
Bone
Tetracycline labeling normal Tetracycline labeling abnormal
biopsy

Treatment

Nonoperative
lifestyle modification & vitamins
indications
calcium and Vitamin D
pharmacologic treatment
indications
2008 National Osteoporosis Foundation Guidelines for Pharmacologic
Treatment of Osteoporosis suggests that pharmacologic treatment be
considered for
postmenopausal women and men >= 50yrs old with:
hip/vertebral fracture
T score between -1.0 and -2.5 at the femoral neck/spine and
10-year risk of hip fracture ≥ 3% or
10-year risk of major osteoporosis-related fracture ≥ 20% by
FRAX calculation
T score -2.5 or less at the femoral neck/spine.
pharmacologic agents
calcium and Vitamin D
bisphosphonates
Conjugated Estrogen-progestin hormone replacement (HRT)
Estrogen-only replacement (ERT)
Salmon calcitonin (Fortical or Miacalcin)
Raloxifene (Evista)
Teriparatide (Forteo)
 Operative
osteoporotic vertebral compression fracture
femoral neck fracture
distal radius fracture

Pharmacologic Agents

Bisphosphonates
1st line therapy
indications for pharmacologic treatment
hip or vertebral fracture
T-score <2.5 at the femoral neck or spine (after exclusion of secondary causes)
low bone mass (T-score between -1.0 and -2.5) and
10-year probability of a hip fracture ≥ 3% or greater or
10-year probability of a major osteoporosis-related fracture ≥ 20% based on
WHO algorithm
mechanism
accumulate at sites of bone remodeling and are incorporated into bone matrix
are released into acid environment once bone is resorbed, and are then taken up
by osteoclasts
decrease osteoclastic bone resorption, flattening of osteoclast ruffled border and
Dec Osteoclast bone resorption
Flattens Osteoclast ruffled border
Inc Osteoclast apoptosis

increased osteoclast apoptosis

renal excretion without undergoing metabolism
exact mechanism depends on presence of nitrogen on alkyl chain (see table
below)
technique
improved rates of treatment when coordinated by treating orthopedic surgeon and
referral to osteoporosis clinic is made
DEXA scan and referral to endocrinologist
outcomes
alendronate reduces the rate of hip, spine and wrist fractures by 50%
risedronate reduces vertebral and nonvertebral fractures by 40% (each) over 3
years
IV zolendronic acid reduces the rate of spine fractures by 70% and hip fractures by
40% over 3 years

Contraindications/
Drug Indications Mechanism Effects Characteristics
Adverse Effects

Calcium
reduces fracture
risk by 34%. daily calcium and
Vitamin D
Vit D
requirements are
supplementation
as follows:
reduces hip
fracture risk by Age 1-3yrs -
10% and 500mg/d
nonvertebral Age 4-8yrs -
prophylactic in all fracture risk by 800mg/d
Calcium & Vit D patients, best for 7%. Age 9-18yrs -
Type II (senile) 1000 to
High dose
1500mg/d
vitamin D
Age >50 yrs-
(median,
1200 to 1500
800IU/d)

reduces hip mg/d calcium

fractures by 800-1,000 IUs
24% and Vit. D
nonvertebral
fractures by
30%.

Esophagitis,
dysphagia,
T score <-2.5SD, gastric ulcers,
Non-nitrogen etidronate,
fragility fracture Produce toxic osteonecrosis of
containing clodronate,
of the hip, in both ATP analog, the jaw (ONJ),
Bisphosphonates tiludronate
men and women atypical
subtrochanteric
fractures

Alendronate
reduces
vertebral
fractures by
48% and
nonvertebral
fractures by
47%.

Risedronate pamidronate,
reduces alendronate
Esophagitis,
Inhibit farnesyl vertebral (Fosamax),
T score <-2.5SD, dysphagia,
pyrophosphate fractures by risedronate
Nitrogen containing fragility fracture gastric ulcers,
synthase 65% and (Actonel),
bisphosphonates of the hip, in both ONJ, atypical
(mevalonate nonvertebral zolendronate
men and women subtrochanteric
pathway) fractures by (Reclast),
fractures
39%. ibandronate
(Boniva)
Ibrandronate
reduces
vetebralfracture
risk by 77%, hip
fractures by
41% and
nonvertebral
fractures by
15%.

Decreased the
risk of hip
fracture, but it
also led to small
in women with increases in a
Conjugated Estrogen-
Type I (within 6 woman's risk
progestin hormone
years of of breast cancer,
replacement (HRT)
menopause) CAD and heart
attack, stroke, PE,
DVT, and
Alzheimer's
disease
Taking
 unconjugated
Estrogen
indicated for estrogen
receptors are
Estrogen-only women with prior (alone) increases
present on
replacement (ERT) hysterectomy the risk of
osteoblasts and
endometrial
osteoclasts
hyperplasia /
uterine cancer)

Men with low Not yet approved

Testosterone levels of by FDA for
testosterone osteoporosis
Women >5y Intranasal -
Binds
postmenopause, Transient rhinitis.
membrane
decreases pain in Injection or nasal Injectable -
Salmon calcitonin receptors on
acute vertebral spray (destroyed nausea, vomiting,
(Fortical or Miacalcin) osteoclasts to
compression by gastric acid) flushing,
inhibit
fractures (acts as hypersensitivity
resorption
neurotransmitter) reactions
Agonist on Selective
estrogen estrogen receptor
receptors in modulator
bone (reduce (SERM), slows
Hot flashes, leg
osteoclast bone resorption
cramps.
resorption). and mild increase
Raloxifene (Evista) Women Contraindicated
Antagonizes in bone thickness.
in patients with
estrogen Reduces risk of
VTE
receptor in vertebral fractures
breast, reducing only (not non-
breast cancer vertebral
risk. fractures).

1-34 amino Transient

Receptors on terminal residues hypercalcemia,
osteoblasts of parathyroid dizziness,
(activates hormone (1-84) nausea,
osteoblasts) ; given headache.
Severe
Teriparatide (Forteo) and renal tubule by daily
osteoporosis/high
cells, also subcutaneous Contraindicated
fracture risk
stimulates injections in Paget's
intestinal (continuous disease due to
absorption Ca infusion leads to potential
and PO4 bone resorption) osteosarcoma
risk

Reduced Arthralgia,
vertebral nasopharyngitis,
Monoclonal Ig2
fractures by back pain,
against RANKL
Postmenopausal 68%, hip SC injection to osteonecrosis of
Denosumab (Prolia) (inhibits binding
women at high fractures by arm, thigh, the jaw
of RANKL to
risk of fracture 40%, abdomen
RANK, like
nonvertebral Contraindicated
osteoprotegerin)
fractures by in severe
20%. hypocalcemia

Humanized
Postmenopausal monoclonal Ig2

women with that activates Reduced new Hyperostosis,

history of Wnt pathway by vertebral cardiovascular
osteoporotic bindsing fracture by 73% events,
Romosozumab (Evenity) fracture, multiple sclerostin SC injection osteoarthritis, and
through month
risk factors for (sclerostin monthly cancer,
12 and by 75%
fracture, or who normally inhibits through month osteonecrosis of
have failed or are Wnt pathway). 24 the jaw, atypical
intolerant to other Promotes bone femoral fracture
osteoporosis formation and
therapy inhibits
resorption.

Complications

Osteonecrosis of the jaw (ONJ) is associated with IV bisphosphonates (but not oral
bisphosphonates)
incidence
rare
treatment
stop bisphosphonates
Atypical subtrochanteric transverse stress fractures (in patients on long-term
bisphosphonates)
incidence
rare
mechanism
extremely low bone turnover rates
shown by reduced markers of bone resorption (e.g. urinary collagen type 1 cross-
linked N-telopeptide, NTx)
treatment
operative fixation with intramedullary nail and stop bisphosphonates

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QUESTIONS (43)

QUESTIONS
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18 of 43

(OBQ12.169) A 72-year-old woman presents with severe hip pain after stepping off of a curb. She
denies any trauma or prior history of hip pain. Her past medical history is reviewed including a list of
her current medications. Which of the following of her medications would place her at increased risk
for a non-traumatic hip fracture? Review Topic | Tested Concept
QID: 4529

1 Phenytoin

2 Cephalexin
 3 Simvastatin

4 Glipizide

5 Allopurinol

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