Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. It is defined by low bone mineral density (BMD) as measured by dual energy x-ray absorptiometry (DXA) scan. Common sites of osteoporotic fractures include the spine, hips, ribs and wrists. The document discusses the mechanisms of bone loss and risk factors for osteoporosis like aging, menopause, low calcium/vitamin D, smoking and corticosteroid use. It outlines approaches to diagnosis, investigation and management including lifestyle modifications, calcium/vitamin D supplementation, bisphosphonates and hormonal therapy.

1. Dr. Muhammad Khairussyakirin b Mohd Ali

2. 
A skeletal disorder characterised by
compromised bone strength predisposing a
person to an increased risk of fracture.
◦ Bone strength reflects the integration of bone
density and bone quality
 Bone density (g/cm2 or g/cm3)
 determined by peak bone mass and amount of bone loss.
 Bone quality
 architecture, turnover, damage accumulation, and
mineralisation of the bone

3. 

The spine, hips, ribs, and wrists are common areas of
bone fractures from osteoporosis.
Classification is based on bone mineral
density (BMD).
◦ Osteoporosis is defined by BMD of less than –2.5
SD from the young adult mean (T-score)

4. 1

5. 
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T score: standard deviation of the BMD from
the average sex matched 35-year-old
For every 1 decrease in T score, double risk
of fracture
1 SD decrease in BMD = 14 year increase in
age for predicting hip fracture risk
Regardless of BMD, patients with prior
osteoporotic fracture have up to 5 times
risk of future fracture!

6. 2

7. 
In our community, the Chinese had the
highest incidence of hip fractures compared
to the Malays and Indians.
◦ Chinese women accounted for 44.8% of hip
fractures

8. 

Bone is continually remodeled throughout our
lives . Bone resorption is always followed by
bone formation, a phenomenon referred to as
coupling
Bone strength is determined by collagenous
proteins (tensile strength) and mineralized
osteoid (compressive strength). The greater
the concentration of calcium, the greater the
compressive strength

9. 

Osteoclasts, derived from mesenchymal cells,
are responsible for bone resorption, whereas
osteoblasts, from hematopoietic precursors,
are responsible for bone formation.
The 2 types of cells are dependent on each
other for production and linked in the
process of bone remodeling

10. 

In osteoporosis a reduction in skeletal mass
caused by an imbalance between bone
resorption and bone formation.
Under physiologic conditions, bone formation
and resorption are in a fair balance. A change
in either—that is, increased bone resorption
or decreased bone formation may result in
osteoporosis.

11. 

Accelerated bone loss can be affected by
hormonal status, as occurs in perimenopausal
women
Aging and loss of gonadal function are the 2
most important factors contributing to the
development of osteoporosis

12. 


Estrogen deficiency accelerates bone loss in
postmenopausal women.
Estrogen deficiency can lead to excessive
bone resorption accompanied by inadequate
bone formation.
Osteoblasts, osteocytes, and osteoclasts all
estrogen receptors.

13. 

In the absence of estrogen, T cells promote
osteoclast recruitment, and prolonged
survival via IL-1, IL-6, and tumor necrosis
factor (TNF)–alpha.
With the prolonged osteoclast survival, rate of
bone resorption will increase.

14. 

In contrast to postmenopausal bone loss,
which is associated with excessive osteoclast
activity, the bone loss that accompanies
aging is associated with a progressive decline
in the supply of osteoblasts in proportion to
the demand.
After the third decade of life, bone resorption
exceeds bone formation

15. 
Calcium and vitamin D help maintain bone
homeostasis. Insufficient dietary calcium or
impaired intestinal absorption of calcium can
lead to secondary hyperparathyroidism. PTH
is secreted in response to low serum calcium
levels. It increases calcium resorption from
bone, decreases renal calcium excretion, and
increases renal production of 1,25dihydroxyvitamin D (1,25[OH]2 D)—an active
hormonal form of vitamin D that optimizes
calcium and phosphorus absorption

16. 
Medications that lead to bone loss (eg,
glucocorticoids) can cause osteoporosis.
Corticosteroids inhibit osteoblast function
and enhance osteoblast apoptosis

17. 
Primary Osteoporosis
◦ Postmenopausal osteoporosis.
 Accelerated bone loss related to oestrogen deficiency
◦ Age-related osteoporosis. This occurs in both men
and women
◦ Idiopathic (rare)

20. 
Most patients are asymptomatic and
diagnosis is made only after a fracture.
Common clinical presentations include:
◦
◦
◦
◦
Increasing dorsal kyphosis
Low trauma fracture
Loss of height
Back pain

21. 
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a careful history, physical examination and
appropriate laboratory investigations, is mandatory
When a patient presents with a low trauma fracture,
osteoporosis is a presumptive diagnosis. BMD (DXA)
is advised.
If absence of this facility, treatment should still be
initiated.
In the absence of a fragility fracture, the gold
standard for the diagnosis of osteoporosis remains
the measurement of BMD using DXA.
If a BMD measurement is not available, calculating
the risk of fractures using Fracture Risk Assessment
Tool (FRAX) can help in deciding treatment strategies.

22. 

FRAX is a fracture risk assessment tool used to
evaluate the 10-year probability of hip and major
osteoporotic fracture risk that integrates clinical
risk factors and bone mineral density at the
femoral neck in its calculations.
Until more Malaysian data are available, it is
recommended to use the Singapore prediction
algorithm.

23. 


A simple clinical screening tool, based on age
and weight, Osteoporosis
OSTA was developed for postmenopausal
Asian women.
Women in the high risk category and those in
the moderate risk category with additional
risk factors (e.g. glucocorticoid use,
hypogonadism, immobilisation) for
osteoporosis should be recommended for
DXA

24. The main aims of investigations are to:
1. Confirm the diagnosis of osteoporosis
2. Assess fracture risk
3. Exclude secondary causes


25. 
Initial investigations include:
1. FBC, ESR
2. Bone profile: serum calcium, phosphate,
albumin
3. Alkaline phosphatase
4. Renal function
5. Plain X-rays - lateral thoraco-lumbar spine
or hip (as indicated)

26. 
clinical suspicion of secondary causes:
◦
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free thyroxine T4 (FT4),
thyroid-stimulating hormone (TSH),
testosterone,
follicle-stimulating hormone (FSH),
luteinizing hormone (LH),
urine Bence Jones protein,
serum protein electrophoresis]

27. 
Densitometry
◦ BMD measurement gives an accurate reflection of
bone mass and helps in establishing the diagnosis
of osteoporosis
◦ use race-specific reference ranges when available
◦ results are reported as
 T-scores (comparison with the young adult mean)
 The risk of fracture is increased two fold for each SD
reduction of T-score in BMD
 Z-scores (comparison with the mean of individuals of
the same age)

28. 
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gold standard for diagnosis
measured at the hip and lumbar spine.
Prediction of fracture risk is site-specific.
◦ If not available, other skeletal sites can be used to
provide an adequate estimation of fracture risk.

Peripheral DXA (phalanges / distal radius /
calcaneum)

29. 

an alternative technique for measuring bone
density in the axial skeleton and vertebral
volumetric bone density
The main limitations are the lack of
availability in Malaysia and a higher radiation
dose compared to DXA

30. 
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to identify patients at high risk of future
fractures.
They should not be used for the diagnosis of
osteoporosis.
used to evaluate treatment efficacy and
compliance to therapy
Changes in level of BTM can be seen within
3-6 months after initiation of drug therapy.

32. 
The aim ::to assess the response to
treatment.
◦ regular clinical assessments
◦ peripheral DXA is not recommended
◦ If biochemical markers are available, two separate
baseline measurements of the same marker need to
be carried out followed by one repeat measurement
2-3 months after initiating therapy and yearly
thereafter, if indicated. These measurements
should be taken at the same time of the day to
minimise the effect of diurnal variation.

33. 
Nutrition
I. Calcium

34. II. Vitamin D
◦ >50 years old or older, the Malaysian
Recommended Nutrient Intake
advocates 400 IU of vitamin D per day,
but many experts recommend at least
800 to 1000 IU per day

35. 

Low body weight and excessive dieting is
associated with low bone mineral status and
increased fracture risk
Maintenance of a BMI >19 kg/m 2 is
recommended for prevention of osteoporosis

36. 

Patients should be advised to limit their
caffeine intake to less than 1 to 2 servings
(240 to 360 mls in each serving) of
caffeinated drinks per day.
Caffeine intake leads to a slight decrease in
intestinal calcium absorption and an increase
in urinary calcium excretion

37. 

Cigarette smoking increases osteoporotic
fracture risk and thus should be avoided
Excessive intake of alcohol should be avoided
because alcohol has detrimental effects on
fracture

38. 
Regular physical activity, in particular weightbearing exercise
◦ (e.g. brisk walking, line dancing) is encouraged in
all age groups in order to maximise peak bone
mass, decrease age-related bone loss, maintain
muscle strength and balance

The individual’s health status should be taken
into consideration when recommending an
exercise programme.

39. o
Most osteoporosis-related fractures,
especially in the elderly, are a consequence of
decreased BMD and falls

40. I. Hormonal therapy (HT)
HT is an effective treatment for
menopausal symptoms that also offers
good protection
for bone.
₋ Estrogen Therapy (with or without
progestin) increases lumbar spine BMD
◦ HT is not recommended in women with
breast cancer, coronary heart disease
or stroke.
⁻

41. 
Bisphosphonates are potent inhibitors of
bone resorption.
◦ Alendronate, risedronate, ibandronate, zoledronic
acid
◦ Two adverse effects have been noted in
bisphosphonate therapy:
 Atypical femoral shaft fractures
 Osteonecrosis of the jaw (ONJ) :exposed, non-vital
bone involving maxillofacial structures, with delayed
healing despite > 8 weeks of appropriate medical care

42. CKD Stages 1-3
 Patients with CKD stages 1-3 and low Tscores or low trauma fractures, most likely
have
osteoporosis. Bisphosphonates can be used
safely.
CKD Stages 4-5
 Bisphosphonates are not recommended for
patients with an estimated GFR < 30 ml/min

43. 

In established osteoporosis, calcium
supplementation alone is not adequate for
fracture prevention. However, calcium
supplementation is necessary for optimal
response to other
treatment modalities

44. 
Activated Vitamin D (calcitriol 0.25 μg bd,
alfacalcidol 1 μg od) has been demonstrated
to increase BMD in those with established
osteoporosis1

45. 

Calcitonin has also been shown
to have an analgesic effect for acute pain in
osteoporosis related vertebral fractures
Side effects of calcitonin include nausea,
flushing, vomiting and nasal irritation.

46. 1.
2.
3.
4.
CPG - Management of Osteoporosis June
2012
Harrison's Principles of Internal Medicine,
18th ed
www.m.webmd.com/a-to-z-guides/bonemineral-density-test.
www.medscape.com/osteoporosis/overview
.