OSTEOPOROSIS
INTRODUCTION
• Osteoporosis defined as a reduction in the strength of bone
that lead to an increased risk of fractures
• WHO- Bone density that falls 2.5 standard deviation (SD)
below the mean for young healthy adults of the same sex
also referred to as a T score of ≤ -2.5
BONE STRUCTURE
• Types of bone
Cortical bone - 80% of total bone
- Dense type of bone that surrounds the
cancellous bone to form outer durable layer.
Cancellous (trabecular) bone
- 20% of total bone
- Interconnected structure of lattice work
porous, spongy inner structure of the bone.
Types of bone cells
Osteoblast, Osteocytes and Osteoclasts
Osteoblast and Osteocytes are derived from mesenchymal
stem cells
During remodelling Osteoblast lay down layers of bone that
add strength to the matrix
Some of the osteoblast are buried in the matrix to become
osteocytes
Osteoclasts originate from hematopoietic stem cells
Osteoclasts are the cells that remove old bone by
dissolving the mineral and breaking down the matrix in a
process called bone resorption
EPIDEMIOLOGY
• Osteoporosis occur more frequently with increasing age as
bone tissue is lost progressively
• More in women as loss of ovarian function at menopause
precipitates rapid bone loss and lower peak bone mass
• In India around 36 million people have osteoporosis
• 1 out of 8 males and 1 out of 3 females in India suffer from
osteoporosis
• Around 80% of people with osteoporosis are women
• While the peak incidence of osteoporosis occur at about
70-80 years of age, in India it may afflict at age of 50-60
years of age
• Osteoporosis is responsible for one and half million
fracture / year
• World wide over 200 million people have
osteoporosis
PATHOPHYSIOLOGY
• Bone remodelling has two primary functions
To repair micro damage within the skeleton to maintain skeletal
strength and relative youth of the skeleton
To supply calcium from the skeleton to maintain serum calcium
• After 30-45 years of age, bone resorption exceeds
formation
• Remodelling may be activated by micro damage to bone as a
result of excessive or accumulated stress
• Osteoblast synthesize and secrete the organic matrix and
regulate new bone formation
• Osteoclasts mainly carried out resorption of bone
• Excessive bone loss can be due to an increase in osteoclastic
activity or decrease in osteoblastic activity
• Nutrition and lifestyle play important role in growth
although genetic factors primarily determine peak skeletal
mass and density
FACTORS REGULATING BONE
REMODELLING
EVENT STIMULATORY FACTOR INHIBITING FACTOR
PARATHYROI OESTROGEN
D
HORMONE
ANDROGEN
CORTISOL
BONE RESORPTION CALCITONIN
THYROXINE
TRANSFORMING GROWTH
PROSTAGLANDINS FACTOR B
INTERLEUKIN 1 INTERFERON
INTERLEUKIN 6 NITRIC OXIDE
EVENT STIMULATORY EFFECT INHIBITORY EFFECT
GROWTH HORMONE CORTISOL
INSULIN LIKE GROWTH FACTOR
TESTOSTE
RONE
BONE FORMATION OESTROGEN
TGF B
SKELETAL GROWTH
FACTOR BONE DERIVED
GROWTH
FACTOR
CALCITONIN
RISK FACTORS
Primary
Previous fracture after age 30 years
Family history of hip fracture
Cigarette smoking
Weight< 127 lb
Low bone mineral density
Secondary Secondary
(non-modifiable) (modifiable)
White race, advanced age Low calcium intake
Poor health Eating disorder
Dementia Low testosterone level
Pre menopausal estrogen deficiency
Excessive alcohol intake
Physical inactivity
Impaired vision
Neurologic disorder
Lack of sunlight exposure
Medical disorder and medication associated
with osteoporosis
• Primary osteoporosis
Juvenile osteoporosis
Post menopausal
osteoporosis
• Endocrine
abnormalities
Glucocorticoid excess
Thyroid hormone
excess
Hypogonadism
Hyperparathyroidism
• Process affecting bone marrow
Multiple myeloma, leukemia, gaucher disease
• Gastrointestinal disorder
Celiac disease, gastrectomy
• Renal insufficiency
• Chronic respiratory disease
• Connective tissue disease
Osteogenesis imperfecta
• Rheumatologic disorder
• Medications
Corticosteroid
Anticonvulsants
Heparin
Methotrexate
Cyclophosphamide, GnRH agonists
Lithium
Cyclosporine
Aluminum
Aromatase inhibitors
CLINICAL FEATURES
• Mostly – asymptomatic
• Acute back pain – due to vertebral fracture
• Gradual onset of height loss and kyphosis with chronic pain
• The pain of VCF can radiate to the anterior chest or
abdominal wall
• Lumbar fractures can be associated with abdominal
symptoms like distension, early satiety and constipation
• Peripheral osteoporotic fractures- local pain, tenderness
and deformity
• Hip fracture, the affected leg is shortened and
externally rotated
INVESTIGATIONS
Dual Energy X Ray Absorptiometry (DXA)
Clinical determination are made of the lumbar spine and hip
T score below -2.5 in the lumbar spine, femoral neck or total
hip has been defined as osteoporosis
It determine mass of bone mineral in the path of the beam
divided by the cross sectional area of the beam expressed as
g/cm2
DXA can be used to obtain lateral images of thoracic and
lumbar spine, a technique called vertebral fracture
assessment(VFA)
If only one skeletal site can be measured it is best to assess
the spine in individuals < 60 years and hip in > 60 years
Indication for BMD testing
• Women aged ≥65 yrs and men aged ≥70; regardless of
clinical risk factors for fracture
• Younger postmenopausal women, women in the
menopausal transition, and men aged from 50 to 69
with clinical risk factors for fracture
• Adults who have fracture at or after age 50
• Adults with a condition (e.g., rheumatoid arthritis) or
taking a medication ( e.g. , glucocorticoids at a daily
dose > 5mg prednisone or equivalent for > 3 months)
associated with low bone mass or bone loss
INDICATIONS FOR VERTEBRAL IMAGING
• All women aged ≥70 yrs and all men aged ≥80 yrs if BMD
T-score at the spine, total hip, or femoral neck is < 1.0
• Women aged from 65 to 69 and men aged from 70 to 79 if
BMD T-score at the spine, total hip, or femoral neck is <1.5
• Postmenopausal women and men aged ≥50 with
specific risk factors:
– Low-trauma fracture during adulthood (aged≥50)
– Historical height loss of ≥1.5 in.(4cm)
– Prospective height loss of ≥0.8 in. (2cm)
– Recent or ongoing long-term glucocorticoid treatment
• BONE BIOPSY
Tetracycline labelling of the skeleton determine rate of
remodelling and evaluation of other metabolic bone diseases.
Not used for diagnosis
• BIOCHEMICAL MARKERS
It provide an earlier estimate of patient response than bone
densitometry
Markers of Bone turnover
Bone Formation Bone Resorption
1. Bone specific alkaline 1.C-terminal cross linked telopeptide of
phosphatase (BAP) type І collagen
2. Osteocalcin 2.N-terminal cross linked telopeptide of
3. C-terminal propeptide of type І
type І collagen
procollagen
3. Hydroxylysine-glycosides
4. N-terminal propeptide of type
І 4. Hydroxyproline
procollagen 5. Pyridinoline
6. Deoxypyridinoline
Indication for Biochemical markers
• Predict risk of fracture independently of bone density
• Predict extent of fracture risk reduction when repeated
after 3-6 months of treatment
• Predict magnitude of BMD increases with therapies
• Predict rapidity of bone loss
• Help determine adequacy of patient compliance to
therapy
• Help determine duration of ‘drug holiday’
• ROUTINE TEST
Complete blood count
Serum and 24 hour urine calcium
Renal and hepatic function test
25(OH)D level
TSH
Urinary free cortisol or fasting serum cortisol
X ray
TREATMENT
• When to start treatment
When there is hip or vertebral fracture (clinical or
asymptomatic)
When BMD is > 2.5 SD below the mean value for young adults
(T score ≤ -2.5) in either spine, total hip or femoral neck
Post menopausal women and men >50 years with fracture risk
factors even if BMD is not in the osteoporosis range
Management of underlying disease
• Risk factor reduction
• Nutritional recommendations
- Calcium: 1200mg/day ,doses of supplements should be <600
mg per single dose
- Vit D: (serum 25(OH) D level should >30 ng/ml)
- recommends daily intake
- Age < 50yrs 200 IU
- 50-70 yrs 400 IU
- >70 yrs 600 IU
• Exercise
Pharmacologic treatment
Antiresorptive Agents
1. Estrogen, Progesteron, Tibolone -
reduce bone turn over, prevent bone loss, and induce small
increase in bone mass (50% )
Act on ERs especially α, inhibit osteoclast
directly and stimulate osteobast to produce paracrine
factor.
Increased risk of fatal and non fatal MI, STROKE, venous
thromboembolism, breast cancer
SELECTIVE ESTROGEN RECEPTOR MODULATORS
1. Raloxifene, Bazedoxifene:
Estrogen antagonist on breast and estrogen agonist on bone,
lipids, clotting factors and endometrium.
Use in pt with low risk of deep vein thrombosis (DVT) and for
whom bisphosphonates or denosumab are not appropriate, or
with a high risk of breast cancer.
Raloxifene 60mg once daily.
BISPHOSPHONATES
• Mechanism of action
Impair osteoclast function and number, in part by
inducing apoptosis
• Side effects
Osteonecrosis of the jaw, subtrochanteric or atypical
fracture
femur
Reduces the incidence of vertebral, hip and
other major fracture by 68%, 40% and
20%.
BISPHOSPHONATES
Alendronate Risedronate Ibadronate Zoledronic acid
DOSE 5-10 mg/day 5mg/day, 150mg/month , 5 mg annually
35mg/wk, 3mg/3month
70mg/weeky 150mg/month
ROUTE Oral oral Oral, IV IV over 15 min
respectivel
y
CALCITONIN
(Dose- 100 IU sc/im daily/weekly, 200 IU nasal spray)
Indicated in post menopausal osteoporosis who cannot tolerate
raloxifene, bisphosphonates, estrogen, denosumab, tibolone,
abaloparatide, or teriparatide or for whom these therapies are
not considered appropriate.
Side effects - nausea, flushing and local irritation, long term use
increase risk of prostate and liver cancer and other malignancy
Suppresses osteoclast
activity by Direct action on
osteoclast calcitonin receptor
Strontium Ranelate
Stimulate calcium uptake in bone while inhibit bone
resorption
Orally administered. Approved by European regulatory
agencies not by FDA
Increased cardiovascular events
DENOSUMAB
( Dose – 60 mg sc every 6 month)
Human monoclonal antibody to the RANKL
Post menopausal osteoporosis with high risk of fracture, Men with
prostrate cancer on GnRH therapy, Women with breast cancer on
aromatase inhibitor
Side effects- hypocalcemia, ONJ, AFF, cellulitis, dermatitis, rashes
Reduces vertebral, hip and non vertebral fracture by 70, 40 & 20%
It bind to RANKL &
inhibit its ability to initiate
formation of mature
osteoclast
ODANACATIB
Cathepsin K inhibitor (an enzyme released from osteoclasts
that degrades collagen I in the bone matrix)
A phase III study (LOFT): 50 mg/day reduces vertebral, hip,
non vertebral fracture by 54%, 47% & 23%
Morphea like skin lesion and atypical femoral fracture were
observed more often in the Odanacatib group
ANABOLIC AGENTS
1. Teriparatide and Abaloparatide (PTH and PTH-Related
Protein Analogs)
Approved for the treatment of osteoporosis in both
men
and women with very high risk and with multiple vertibral
fracture
Dose- 20-40 mcg/day sc injection
PTH stimulates wnt, IGF-I and
collagen production and increase osteoblast
number by replication and inhibiting
apoptosis
Effect of parathyroid hormone treatment
Side effects- leg cramps, muscle pain, weakness, dizziness, headache and nausea
Reduces vertebral and non vertebral fractures by 65 and 45%
Treatment of patients with osteoporotic
fracture
Depending on the location and severity of the fractures
procedures may include open reduction and internal
fixation, hemiarthroplasty and total arthroplasty
Long bone fractures often require either external and
internal fixation
Vertebral, rib and pelvic fracture usually managed with
supportive care requiring no specific orthopaedic treatment
Treatment monitoring
BMD is considered as a monitoring tool, should be repeated at
intervals> 2 years
Changes must exceed 4% in the spine and 6% in the hip to be
considered significant in any individual
Biochemical marker of bone turnover may prove useful for
treatment monitoring
Determination should be made before therapy is started and
repeated > 4 month after therapy
Change in bone turnover markers must be 30-40% lower than
the baseline to be significant
Preventive measures
Reducing risk factors for bone loss(hypogonadism, decreased
body fat, cigarette smoking, inactivity, alcohol intake)
Patient should be advised to consume adequate vitamin D and
calcium
Patient should be advised to participate in a regular weight
bearing exercise
Avoid caffeine
THANK YOU
