MSS disorders cont’d…

Metabolic Bone Disorders

1. Osteoporosis
Osteoporosis is the most prevalent bone disease in the world.
It is a disease characterized by:
 Low bone mass
 Micro architectural deterioration of the bone tissue
 Leading to:
o Enhanced bone fragility
o Increase in fracture risk
The consequence of osteoporosis is bone fracture.
Peak adult bone mass is achieved between the ages of 18 & 25
years in both females and males and is affected by genetic factors.
Bone mass during these years is affected by nutrition, physical
activity, medications, endocrine status, & general health .

3
 Types and causes of osteoporosis
 Primary osteoporosis
 Occurs
 In women after menopause (usually between

the ages of 45 and 55 years) &

 In men later in life, but it is not merely a

consequence of aging.
 Failure to develop optimal peak bone mass

during childhood, adolescence, & young

adulthood contributes to the development of
osteoporosis.

3
Cont’d...
Focus on prevention by
 Early identification of at-risk teenagers & young adults,
 Increased calcium intake,
 Participation in regular weight-bearing exercise, and
 Modification of lifestyle (e.g., reduced use of caffeine,
cigarettes, carbonated soft drinks, and alcohol)

o The above are interventions that decrease the risk of

osteoporosis, fractures, & associated disability later in life.

4
Cont’d...
 Secondary osteoporosis
 Is the result of medications or other conditions
& diseases that affect bone metabolism.
 Specific disease states (e.g., hypogonadism)

 Medications (e.g., corticosteroids, antiseizure

medications) &
 Metabolic problem

 The degree of osteoporosis is related to the

duration of medication therapy.

5
FIG. - Risk factors for osteoporosis, and their effects on
bone remodelling and maintenance.
Genetics
• Caucasian or Asian • Predisposes to low
• Female bone mass
• Family history
• Small frame
Age
• Post menopause • Hormones (estrogen,
• Advanced age calcitonin, & testosterone)
leads to bone loss
• Low testosterone in men
• Decreased calcitonin
Nutrition
• Low calcium intake
• Low vitamin D intake • Reduces nutrients
• High phosphate intake (carbonated needed for bone
beverages) remodeling
• Inadequate calories
6
Cont’d....
Physical exercise
• Sedentary • Bones need stress for bone
• Lack of weight-bearing exercise maintenance
• Low weight and body mass index

Lifestyle choices
• Caffeine • Reduces osteogenesis in
• Alcohol
bone remodeling
• Smoking
• Lack of exposure to sunlight

Medications
 e.g., corticosteroids, antiseizure
medications, heparin, thyroid hormone • Affects calcium absorption
Co-morbidity and metabolism
 e.g., anorexia nervosa, hyperthyroidism,
malabsorption syndrome, renal failure

7
Pathophysiology
Osteoporosis is characterized by
 Reduced bone mass,
 Deterioration of bone matrix, and
 Diminished bone architectural strength.
 Normal homeostatic bone turnover is altered;
 The rate of bone resorption that is maintained by

osteoclasts is greater than the rate of bone formation that

is maintained by osteoblasts,
 Resulting in a reduced total bone mass.

 The bones become progressively porous, brittle, & fragile;

 They fracture easily under stresses that would not break

normal bone.
 These fractures may be the first clinical manifestation of
osteoporosis.

8
p/p cont’d...
 These increase susceptibility to fracture, which
occur most commonly as(presented as)
 Compression fractures of the thoracic and lumbar

spine, hip fractures, & fractures of the wrist.


Gradual collapse of a vertebra may be
asymptomatic; it is observed as progressive
kyphosis.
 There is an associated loss of height.

 The postural changes result in relaxation of the

abdominal muscles & a protruding abdomen.

 The deformity may also produce pulmonary

insufficiency.
9
Gerontologic Considerations
 The prevalence of osteoporosis in women older than 80 years is 50%.
 The average 75-year-old woman has lost 25% of her cortical bone and 40% of her

trabecular bone.
 With the aging of the population, the incidence of fractures (more than 1.5 million

osteoporotic fractures per year), pain, & disability associated with osteoporosis is
increasing.
 Elderly men are also at heightened risk for osteoporosis and fractures.
 Men are more likely than women to have secondary causes of osteoporosis that may
lead to fractures,
 Possibly due to
 use of corticosteroids (e.g., prednisone) and
 excessive alcohol intake.
 Elderly people absorb dietary calcium less efficiently and excrete it more readily
through their kidneys;
 Therefore, postmenopausal women & the elderly need to consume approximately

1200 mg of daily calcium;

 Quantities larger than this may place patients at heightened risk for renal calculi

(i.e., kidney stones) or cardiovascular disease.

10
Cont’d...
 Age-related loss begins soon after the peak bone mass
is achieved (i.e., in the fourth decade).
 Calcitonin, which inhibits bone resorption and

promotes bone formation, is decreased.

 Estrogen, which inhibits bone breakdown, decreases

with aging.
 PTH increases with aging, increasing bone turnover

and resorption.
 The consequence of these changes is net loss of bone
mass over time.

11
Cont’d...
 Women develop osteoporosis more frequently
and more extensively than men b/c of
 Lower peak bone mass and

 The effect of estrogen loss during

menopause.

 More than half of all women older than 50 years

show evidence of osteopenia.

12
Assessment & Diagnostic Findings
 Osteoporosis may be undetectable on routine x-
rays until there has been 25% to 40%
demineralization, resulting in radiolucency of the
bones.

 Osteoporosis is diagnosed by dual-energy x-ray

absorptiometry (DXA), which provides information
about BMD at the spine and hip.

 The DXA scan data are analyzed and reported as

T-scores (the number of standard deviations [SDs]
above or below the average BMD value for a
young, healthy Caucasian woman). 13
Cont’d...
BMD testing is recommended for
 All women older than 65 years of age,

 All men older than 70 years of age,

 Postmenopausal women and

 Men older than 50 years of age with osteoporosis risk factors, and

 For all people who have had a fracture thought to occur as a

consequence of osteoporosis.
 BMD studies are useful in identifying osteopenic & osteoporotic bone and in

assessing response to therapy.

 Through early screening (using both assessment of risk factors and BMD

scans),
 Promotion of adequate dietary intake of calcium & vitamin D,
 Encouragement of lifestyle changes, and
 Early institution of preventive medications,
 Bone loss and osteoporosis can be reduced,
 Resulting in a reduced incidence of fracture.

14
On P/E
 Height loss
 Body weight  Skin fold thickness
 Kyphosis  Arm span-height difference
 Tooth loss  Wall- occiput distance
 Rib-pelvis distance

15
Cont’d...
 Laboratory studies (e.g., serum calcium, serum
phosphate, serum alkaline phosphatase, urine
calcium excretion, urinary hydroxyproline
excretion, hematocrit, erythrocyte sedimentation
rate [ESR]) and x-ray studies
 Are used to exclude other possible disorders

(e.g., multiple myeloma, osteomalacia,

hyperparathyroidism, malignancy) that
contribute to bone loss.

16
Management aspects
 A diet rich in calcium & vitamin D throughout life,
 An increased calcium intake during adolescence, young adulthood, & the
middle years, protects against skeletal demineralization.
 Such a diet includes three glasses of whole vitamin D–enriched milk or
other foods high in calcium (eg, cheese & other dairy products, steamed
broccoli, canned salmon with bones) daily.
 Regular weight-bearing exercise promotes bone formation.
 From 20 to 30 minutes of aerobic exercise (e.g., walking), 3 days or more
a week, is recommended.
 Weight training stimulates an increase in BMD.
 Exercise improves balance, reducing the incidence of falls and fractures.

17
Available Pharmacologic Therapy
 Calcium and vitamin D
 Hormone replacement therapy
 Selective estrogen receptor modulators ( SERMs )
 Bisphosphonates
 Calcitonin
 Parathyroid hormone

18
Cont’d...
 The first-line medications used to treat and prevent
osteoporosis include
 Calcium & vitamin D supplements &

bisphosphonates.
o To ensure adequate calcium intake, a calcium
supplement (eg, Caltrate, Citracal) with vitamin D may be
prescribed and taken with meals or with a beverage high
in vitamin C to promote absorption.
o Common S/E of calcium supplements are abdominal distention &
constipation.
 Calcitonin, selective estrogen receptor modulators,
and anabolic agents.

19
Cont’d...
 Bisphosphonates that include daily or weekly oral preparations of
alendronate (Fosamax) or risedronate (Actonel), monthly oral
preparations of ibandronate (Boniva), or yearly intravenous (IV)
infusions of zoledronic acid (Reclast) increase bone mass and decrease
bone loss by inhibiting osteoclast function .
 W/c prevents osteoporotic-related fractures in women 65 years of

age and older.

 Alendronate is very effective therapy in preventing fractures in
postmenopausal women with osteoporosis.
 Adequate calcium and vitamin D intake is needed for maximum effect,
but these supplements should not be taken at the same time of day as
bisphosphonates.
 Side effects of bisphosphonates include gastrointestinal symptoms

(eg, dyspepsia, nausea, flatulence, diarrhea, constipation).

 Some patients may develop esophageal ulcers, gastric ulcers, or

osteonecrosis of the jaw related to bisphosphonate use.

20
Cont’d...

 Calcitonin directly inhibits osteoclasts,

thereby reducing bone loss & increasing
BMD.
 Calcitonin is administered by nasal spray or by
SC or IM injection.
 S/E include nasal irritation, flushing,
gastrointestinal disturbances, and urinary
frequency.
 It should not be prescribed for patients with
seafood allergies.
21
Cont’d...
o Selective estrogen receptor modulators (SERMs),
such as raloxifene, reduce the risk of osteoporosis
by preserving BMD without estrogenic effects on
the uterus.
o They are indicated for both prevention and treatment of
osteoporosis.
o They are C/I in women with a history of venous
thromboembolism.
o Teriparatide (Forteo) is a subcutaneously
administered anabolic agent that is administered
once daily. As a recombinant PTH, it stimulates
osteoblasts to build bone matrix and facilitates
overall calcium absorption.
22
Cont’d....
Fracture Management
 Fractures of the hip that occur as a

consequence of osteoporosis are managed

surgically by joint replacement or by closed or
open reduction with internal fixation (eg, hip
pinning)
 Osteoporotic compression fractures of the

vertebrae are managed conservatively.

Additional vertebral fractures and progressive
kyphosis are common.
 Pharmacologic and dietary treatments are

aimed at increasing vertebral bone density.

23
24
-

B) Osteomalacia
 Osteomalacia is a metabolic bone disease

characterized by inadequate mineralization of

bone.
 As a result of faulty mineralization, there is

softening and weakening of the skeleton, causing

pain, tenderness to touch, bowing of the bones,
and pathologic fractures.
 w/n osteomalacia is combines with osteoporosis

the incidence of fracture is high.

Cont---
 Osteomalacia is adult equivalent of rickets or vitamin
D deficiency diseases in children.
 On physical examination, skeletal deformities (spinal
kyphosis and bowed legs) give patients an unusual
appearance and a waddling/walking side to side or
limping gait.
 These patients may be uncomfortable with their
appearance.
 As a result of calcium deficiency, muscle weakness,
and unsteadiness, there is an increased risk for falls
and fractures.
Pathophysiology

 The primary defect in osteomalacia is a

deficiency of activated vitamin D (calcitriol),
which promotes calcium absorption from the
gastrointestinal tract and facilitates
mineralization of bone.
 Without adequate vitamin D, calcium and
phosphate are not moved to calcification sites
in bones
Cont---
 Osteomalacia may result from failed calcium
absorption (eg, mal absorption syndrome) or from
excessive loss of calcium from the body.
 Gastrointestinal disorders (eg, celiac disease, chronic
biliary tract obstruction, chronic pancreatitis, small
bowel resection) in which fats are inadequately
absorbed are likely to produce osteomalacia through
loss of vitamin D and calcium.
 Liver and kidney diseases can produce a lack of
vitamin D because these are the organs that convert
vitamin D to its active form.
Cont---

 Severe renal insufficiency results in acidosis. The

body uses available calcium to combat the
acidosis, and PTH stimulates the release of
skeletal calcium in an attempt to reestablish a
physiologic pH.
 During this continual drain of skeletal calcium,
bony fibrosis occurs and bony cysts form.
 Hyperparathyroidism leads to skeletal
decalcification and thus to osteomalacia by
increasing phosphate excretion in the urine.
Cont---
 Prolonged use of antiseizure medication (eg,
phenytoin, phenobarbital) poses a risk for
osteomalacia.
 The malnutrition type of osteomalacia (deficiency in
vitamin D often associated with poor intake of
calcium) is a result of poverty, food faddism, and
lack of knowledge about nutrition.
 It occurs most frequently in parts of the world
where vitamin D is not added to food, where dietary
deficiencies exist, and where sunlight is rare.
Assessment and Diagnostic Findings

 On x-ray, generalized demineralization of

bone is evident. Studies of the vertebrae may
show a compression fracture with indistinct
vertebral end-plates.
 Laboratory studies show low serum calcium
and phosphorus levels.
 Urine excretion of calcium and creatinine is
low.
Medical Management

 The underlying cause of osteomalacia is

corrected if possible.
 If osteomalacia is caused by malabsorption,
increased doses of vitamin D, along with
supplemental calcium, are usually prescribed.
 Exposure to sunlight for ultraviolet radiation to
transform a cholesterol substance (7-
dehydrocholesterol) present in the skin into
vitamin D may be recommended.
Cont---

 If osteomalacia is dietary in origin, a diet with

adequate protein and increased calcium and
vitamin D is provided.
 The patient is instructed about dietary sources of
calcium and vitamin D (eg, fortified milk and
cereals, eggs, chicken, livers).
 The safe use of supplements is reviewed.
Because high doses of vitamin D are toxic and
enhance the risk of hypercalcemia, the importance
of monitoring serum calcium levels is stressed.
Cont---

 Prognosis: Frequently, skeletal problems

associated with osteomalacia resolve
themselves when the underlying nutritional
deficiency or pathologic process is
adequately treated.
Cont---

 N.B. osteomalacia and osteoporosis share

similar characteristics but have different
features i.e.
 Osteomalacia is demineralization of bone
whereas osteoporosis is decrease in density
of bone.
 Osteoporosis is due to lacks of calcium and
osteomalacia due to lacks of vitamin D.