OSTEOPOROSIS, RICKETS,

OSTEOMALACIA
HIN, DUL
 Low Bone Mass

OSTEOPOROSIS

Defects in Bone
Structure
The incidence of fractures of the vertebrae, hip and
wrist rises progressively after the menopause
 RISK FACTORS
Age

Female

Previous fragility fracture

Frequent use of systemic glucocorticoids

Family history of hip fracture

Low BMI (<18.5 kg/m2)

Smoking

Alcohol intake
 CLASSIFICATION

Primary Osteoporosis (Type I)

Secondary Osteoporosis (Type II)

POST MENOPAUSAL OSTEOPOROSIS
(TYPE 1)

Lost of estrogen and androgen

increased bone turn over

bone resorption > bone formation, predominant loss

of trabecular bone compared with cortical bone
Clinical features
• Asymptomatic
• Fracture caused by low
energy trauma
Dowager’s hump
• Kyphotic deformity of
the thoracic spine in
patient with
osteoporosis
 Diagnostic

Plain X-rays can’t diagnose osteoporosis

MILD (20-25% height

Systematic reduction)
approaches to
MODERATE (25-40%
Osteoporotic height reduction)
vertebral Future hip fractures
fractures SEVERE (>40% height
reduction)
Fracture risk
Assessment
Clinical risk factors
+
Bone density
 Prevention

DXA

Life Style Modification

(diet rich in calcium and vitamin D, weight bearing
physical activity, and to avoid smoking and alcohol)
 Treatment

Goal of
Treatment

To reduce risk of
future fracture
Bisphosphonates

• First line medication

Denosumab

• Antibody to RANKL
• Subcutaneous injection given every 6
months
Parathyroid hormone

•Preotact and Teriparatide

(recombinant human parathyroid
hormone 1-34)
•Given intermittenly, low doses
•Stimulate bone formation
Selective estrogen receptor mudulators (SERMs)

• Raloxifene
• (+) reduce the risk of vertebral fracture
• (-) hot flushes

Strontium ranelate

• Increase bone formation, reduce bone resorption

• Sachet of granules to be dissolved in water, drunk once per
day
Cathepsin K inhibitor

•Odanacatib
•A lysosomal cysteine proteinase
with high collagenase activity
Glucocorticoid-induced Osteoporosis
Gonadal Hormone Insufficiency
Women (oestrogen lack)

• Young women post oophorectomy

• Pubertal girls with ovarian agenesis and amenorrhea (Turner’s
syndrome)
• Amenorrheic female athletes
• Adolescent with anorexia nervosa

Men

• >70 years of age (decreased testicular function)

• Young men with hypogonadism
 Hyperthyroidism
Untreated hyperthyroidism  bone resorption >>
formation

Fractures occur in elderly with menopause +

hyperthyroidism

The worst cases  spontaneous fractures, ↑

serum alkaline phosphatase, hypercalcaemia,
hypercalciuria

Treatment  treat both osteoporosis and

thyrotoxicosis
Multiple Myeloma and Carcinomatosis

Overproduction of local osteoclast-activating factors

 bone loss
 Alcohol Excess

↓ calcium absorption

Liver failure

Toxic effect on osteoblast function

 Immobilization

Bone resorption >> formation  hypercalcaemia,

hypercalciuria, severe osteoporosis

Encouraging mobility, exercise and weight-bearing can help

decreasing the effects
Obesity
 Diabetes

Type 1 DM  risk of osteoporosis increased

Type 2 DM  Diabetic bone disease (related to poor bone

quality caused by hypercalcaemia, diabetic complications or
other lifestyle factors)
Biphosphonates rule in
Osteoporosis
 Biphosphonates

Primary agents in the current pharmacological against

osteoclastmediated bone loss due to osteoporosis

The leading clinical intervention for postmenopausal

osteoporosis because of the ability of bisphosphonates to
selectively suppress osteoclast activity and thereby retard bone
resorption.
 Mechanism of action
Tissue level
• reduction of bone turnover

Cellular level
• inhibition of osteoclastic activity on the bone surface
• inhibition of osteoclast recruitment on the bone surface
• osteoclast apoptosis

Molecular level
• Interferes with osteoclast intercellular biochemical pathway
• Inhibition of farnesyl phyrophosphate synthase
• Metabolized to toxic analogue of ATP (non-nitrogen containing
BP’s)
 Pharmacodinamic

1. Distribution: Rapid accumulation in sites of

increased bone deposition/resorption, low
plasma levels, ½ life of “years”
2. Metabolism: Not metabolized (nitrogen
containing)
3. Excretion: Renal
 Administration
• Maximum effect occurs after 3 month initiation
therapy in daily
• The most potent bisphosphonate, zoledronic acid, at a
dose of either 4 mg or 5 mg.
• Oral bisphosphonate therapy was poor resorbed
• Acute phase reaction is increased in patients receiving
IV
• The more recent development of pharmacologically
equivalent preparations allowing for once weekly
(alendronate or risedronate) or even monthly
(ibandronate or risedronate) oral administration
 Administration
• Available as daily, weekly and monthly oral
preparations and 3 monthly and yearly
injections
• Daily and weekly- alendronate, risedronate,
etidronate
• Monthly- ibandronate
• 3 monthly IV- ibandronate infusion
• Yearly IV- zoledronate infusion
 Bisphosphonates: Mechanism of Action and Role in Clinical Practice
Matthew T. Drake, MD, PhD, Bart L. Clarke, MD, and Sundeep Khosla, MD
Ricketsia and Osteomalacia
• Two different expression of the same disease,
inadequate mineralization of bone, in children
called rickets, in adult called osteomalacia
• Osteoid throughout sceleton is incompletely
calcified, and the bone is softened
“osteomalacia”
• Vitamin D resistent rickets/osteomalacia is
caused by phophatase deficiency
 Pathology
• Rickets is inability to calcify the intercellular
matrix in the growth plate
• Osteomacia is widened osteoid stems and
thinner cortices
 Clinical Features
• Child
 Parents notice a failure to thrive, listlessness, muscular
falccidity
 Enlargement of the costochondral junctions (rickety
rosary)
 Lateral indentation of the chest (Harrison Sulcus)
 Coxa vara and bowing femur and tibia
• Adult
 Widespread bone pain and muscle weakness
 Unexplained pain in hip or long bones
 Muscle weakness ( waddling gait )
X Ray
 X ray
• Child
Thickening and widening of growth plate
Bowing of the diaphysis
• Adult
Indentation
Looser zone
Biconcave appereance
 Biochemistry and Bone biopsy

• Raised level of PTH and

ALP with reduced serum
phosphate
• A very low 25-OHD level
(<10 nmol/L)
• A decrease in the rate of
bone turnover and an
increase in the amount
of uncalcified osteoid.
 Treatment
• Vit D supplementation
• 300-600000 IU initial dose
• available at 10 000 and 50 000 IU doses
• the bioavailability of vitamin D following IM
depo injections has been called into question,
and use of high-strength oral vitamin