The document provides a comprehensive overview of musculoskeletal disorders, particularly focusing on osteoporosis, its epidemiology, risk factors, pathophysiology, and management strategies. It highlights the relationship between bone density, bone strength, and fracture risk, while detailing various pharmacologic and non-pharmacologic treatment options. Additionally, it discusses the significance of calcium and vitamin D, as well as anti-resorptive therapies in maintaining bone health and preventing osteoporosis-related fractures.

1. Musculoskeletal disorders
Pharmacotherapy
Tirsit Ketsela (B.pharm, MSc in Clinical Pharmacy)
December 2024
12/29/24 1

2. Contents
•Osteoporosis -Bones become weak and brittle.
•Osteoarthritis-degeneration of joint cartilage and
underlying bone
•Rheumatoid arthritis - Inflammation in the joints
•Gout and hyperuricemia- Too much uric acid in
the body.
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3. Osteoporosis
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4. Introduction
•A Greek term ----- Osteoporosis
• Osteo --- bone
•porosis --- porous/ having space or
hole
•a bone disorder characterized by low
bone density, impaired bone
architecture, and compromised bone
strength that predisposes a person to
increased fracture risk
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5. Cont.….
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6. Cont.….
•It weakens bones to the point that they
can break easily.
• usually occurs a bone in the hip, spine,
or wrist.
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7. 12/29/24 7

8. Epidemiology
•Low bone density/osteopenia and
osteoporosis are very common and
affect all races and ethnic groups.
•Low bone density is estimated to occur
in women age 50 and older.
•53% of non-hispanic white,
•48% of mexican american, and
•36% of non-hispanic black
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9. Cont.…
•Osteoporosis affects women age 50 and older
•16% of non-hispanic white,
•20% of mexican american, and
•8% of non-hispanic black.
•Disease prevalence greatly increases with age
•from 7% in women 50 to 59 years of age to 35% in
women 80 years of age and older
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10. Cont.…
•Approximately 35% of men aged 50 years and
older have low bone density rising to 53% in men
80 years and older.
•Osteoporosis prevalence in men
•Non-hispanic white men is 4%,
•Mexican american men is 6%,
•Non-hispanic black men is 1%
•Osteoporosis prevalence rises to 11% in men 80
years and older.
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11. Cont.…
•Fragility wrist and vertebral fractures are common
throughout adulthood, with hip fractures more
common in older adults.
•While women experience the majority of fractures,
approximately 29% to 40% of fractures occur in
men
•One of two women and one of five men will have a
fracture in their life.
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12. Etiology
•The major risk factors influencing bone loss
are
•Hormonal status
•Genetics
•Exercise
•Aging
•Nutrition, lifestyle
•Concomitant diseases, and medications.
•Non hormonal risk factors are similar
between women and men.
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13. Cont.…
1. Low bone mineral density
2. Female sex
3. Advanced age
4. Race/ethnicity
5. History of a previous fragility (trauma) fracture as
an adult
6. Low body weight or body mass index
7. Premature menopause (before 45years old)
8. Secondary osteoporosis
9. Rheumatoid arthritis
Risk Factors for Osteoporosis and Osteoporotic Fractures
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14. Cont.…
10. Past or present systemic oral glucocorticoid
therapy
11. Low calcium intake
12. Low physical activity or immobilization
13. Vitamin D deficiency
14. Cognitive impairment
15. Impaired vision
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15. Medications
1)Anti seizure therapy ( e.g phenytoin,
carbamazepine, phenobarbital, and valproic
acid)
2)Antiretroviral therapy (e.g TDF)
3)Calcineurin inhibitors (eg, cyclosporine and
tacrolimus)
4)Furosemide
5)Glucocorticoids
Cont.…
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16. 12/29/24 16

17. Cont.…
Bone mineral density/ BMD
•A measure of the amount of minerals
contained in a certain volume of bone
•It is a major predictor of fracture risk.
•T-score between +1 and -1 A t-score of -1.0 or
above is normal bone density
•Low BMD can occur as a result of failure to
reach a normal peak bone mass.
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18. Cont.…
•Women and men begin to lose a small
amount of bone mass starting in the third to
fourth decade of life, about 0.5% to 1% per
year.
•During perimenopause and menopause, bone
loss occurs predominantly due to increases in
bone resorption.
•By age 70 to 80, 30% to 40% of bone mass is
lost in women.
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19. Cont.…
Bone strength
•is highly affected by the quality of the bone’s
composition and its structure, and is a better
predictor of fracture than BMD
•Known by using x-rays, dual-energy x-ray
absorptiometry (DEXA or DXA), or a special CT
scan that uses computer software to
determine bone density
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20. Pathophysiology
•Bones are made of living tissue. To keep them
strong, a healthy human body breaks down old
bone and replaces it with new bone.
•Bone remodeling ----- a lifelong physiological
process where old or damaged bone is replaced
with new bone to maintain
•skeletal strength,
•adapt to mechanical stress,
•regulate calcium and phosphate levels in the
body.
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21. Cont.….
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22. Cont….
Postmenopausal osteoporosis
• Estrogen stimulates the bone-building cells called
osteoblasts. New bone cells will replace old dead
cells.
•It is a critical regulator of bone remodeling. Its
deficiency shifts the balance toward excessive
bone resorption, leading to osteoporosis.
• women begin to produce lower levels of estrogen
as they age and stop during menopause
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23. Cont.…
•Estrogen deficiency
• causes significant bone density loss and
compromises bone architecture.
• increases proliferation, differentiation, and
activation of new osteoclasts and prolongs
survival of mature osteoclasts
•increases calcium excretion and decreases
calcium absorption
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24. Cont.…
Male osteoporosis
•Men are at a lower risk for developing
osteoporosis and fractures because of
Larger bone size
Greater bone mass
 fewer falls
Shorter life expectancy
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25. cont.
Age-related osteoporosis
•About 0.5% BMD is loss each year after
age 30 years, increasing to 1.6% after 85
years.
•It occurs in older adults because of
accelerated bone turnover rate and
reduced osteoblast bone formation
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26. cont.
•These bone changes occur from
Hormone deficiencies
Calcium and vitamin D deficiencies
due to changes in intake and
absorption
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27. Cont.…
Medication-induced secondary causes of
osteoporosis
•Common secondary cause of
osteoporosis.
•Alternative medications should be used
when possible, with consideration given
to patients’ individual risk and baseline
BMD status.
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28. Cont.…
•When these medications cannot be
avoided assessment of benefits and risks
should be performed
•Two of the most common causes of
medication-induced osteoporosis are
glucocorticoids and certain cancer
chemotherapies
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29. Clinical Presentation
• General
•Many patients are unaware they have
osteoporosis until testing or fracture.
•Fractures can occur after bending, lifting, or
falling, or independent of any activity.
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30. Cont.…
• Symptoms
• Frequently asymptomatic
•Pain, Immobility
•Depression, fear, and low self-esteem from
physical limitations and deformities
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31. Cont.…
•Signs
•Shortened stature (>4 cm loss from
maximum height; >2 cm in 1 year),
kyphosis, or lordosis
•Fragility ,vertebral, hip, wrist, or forearm
fracture
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32. diagnosis
Laboratory tests
•Routine tests: comprehensive metabolic profile
(creatinine, calcium, phosphorous, electrolytes,
alkaline phosphatase, and albumin, vitamin D,
thyroid-stimulating hormone)
•Bone turnover markers (eg, urinary or serum NTX,
serum CTX, and serum PINP) are sometimes used,
especially to determine if high bone turnover exists.
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33. Cont.…
• Other diagnostic tests
Spine and hip bone density measurement
using central dual-energy x-ray
absorptiometry (DXA)
Radiograph ordered for other reasons that
shows low bone density
Radiograph to confirm fracture
Balance and mobility tests
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34. Management
•To reduce the future incidence of
osteoporosis.
•To stabilize or improve bone mass and
strength
•To prevent fractures
•To reduce pain and deformity
•improving functional capacity and quality of
life
Goals
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35. Cont.…
General approach
• The treatment Involves
•treating fractures
•preventing fractures
•using medicines to strengthen bones.
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36. Cont.…
•A bone-healthy lifestyle should begin at
birth and continue throughout life
•Supplements and medications are used
when lifestyle habits are insufficient
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37. Cont.…
Non-pharmacologic
•Bone-healthy lifestyle includes
•well balanced diet with calcium,
vitamin D and protein
•exercise
• fall prevention
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38. Cont.….
•Calcium and vitamin D
• Adequate calcium intake is necessary for
calcium homeostasis throughout life, bone
development during growth, and bone
maintenance
•The three main sources of vitamin D are
sunlight (conversion of 7-
dehydrocholesterol to vitamin D3), diet,
and supplements.
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39. Cont.…
Exercise
•It can decrease the risk of falls and fractures
by stabilizing bone density and improving
muscle strength, coordination, balance, and
mobility.
•Exercise, including weight-bearing
activities, at least three to four times
weekly for 30 to 40 minutes per session
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40. Cont.…
Pharmacologic therapy
•is considered in any postmenopausal woman
or man age 50 years and older presenting with
one of the following scenarios:
1. A hip or vertebral fracture
2. T-score of −2.5 or lower at the femoral
neck, total hip, or spine
3. Low bone mass (t-score between −1.0
and −2.5 at the femoral neck, total hip,
or spine)
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41. Algorithm for the management of osteoporosis
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42. Cont.…
Anti resorptive therapies
•Bone resorption is the destruction of bone
tissues that promotes bone loss----a decrease
in bone mass and bone density.
Calcium
Vitamin D
Bisphosphonates
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43. Cont.…
Estrogen agonists/antagonists (EAA),
Tissue selective estrogen complexes
(TSEC),
Calcitonin, parathyroid hormone analogue
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44. Cont.….
1. Calcium Supplementation
•Calcium is the main mineral found in bone
•Its imbalance can result from inadequate
dietary intake, decreased calcium absorption,
enhanced calcium excretion, and diseases
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45. Cont.….
•Adequate calcium intake is used for
prevention and treatment and should be
combined with vitamin D
•If dietary intake cannot be increased to
achieve adequate intake, calcium
supplements can be used.
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46. Cont.….
•Adverse effects
•constipation, can first be treated with
increased water intake, dietary fiber, and
exercise., If still unresolved, smaller and
more frequent administration or a lower
total daily dose can be tried.
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47. Cont.….
•Calcium carbonate can create gas and cause
upset stomach.
•Calcium citrate, a formulation with fewer GI
side effects, is often recommended if calcium
carbonate is not tolerated.
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48. Cont.…..
•500 to 600 mg per day of elemental calcium are
recommended
• Calcium carbonate contains elemental calcium (40%) and is
typically the least expensive.
•should be taken with meals, which increases gastric
acidity resulting in product dissolution
•Calcium citrate (21% elemental calcium) has acid-
independent absorption and does not need to be
administered with meals
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49. Cont.….
2. Vitamin D Supplementation
•Vitamin D helps the body absorb calcium.
•Supplemental vitamin D given at doses of 700 to
800 units per day has been shown to significantly
reduce the incidence of both hip and non vertebral
fractures
•Small increases in BMD, improvement in muscle
strength, and improvement in balance have also
been
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50. Cont.….
3. Bisphosphonates
•They slow the rate that bone is broken
down in body. This maintains bone density
and reduces risk of a broken bone.
•The bisphosphonates inhibit bone
resorption.
•Alendronate
•Risedronate
•Ibandronic acid
•Zoledronic acid
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51. Cont.….
•Alendronate, risedronate, and intravenous
zoledronic acid
•Are approved for postmenopausal, male, and
glucocorticoid-induced osteoporosis.
•Intravenous and oral ibandronate and some
specialized oral formulations of other
bisphosphonates
•Are indicated only for postmenopausal
osteoporosis.
•Bisphosphonates mimic pyrophosphate, an
endogenous bone resorption inhibitor.
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52. Cont.….
•Oral bisphosphonate bioavailability is less than 1%;
and is greatly decreased with concomitant food and
beverages
•Bisphosphonates differ in the strength of binding to
bone (zoledronic acid > alendronate > ibandronate
> risedronate)
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53. Cont.…
•Adverse effect
•GI complaints, including heartburn and dyspepsia, which
are one of the most common reasons cited by patients
for discontinuing therapy
•Less common but severe: esophageal erosion, ulcer, or
GI bleeding
•Intravenous zoledronic acid or ibandronate can be used
for patients with GI contraindications or intolerances to
oral bisphosphonates.
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54. Cont.….
•Contraindications
•creatinine clearances (crcl) less than 30 to 35 ml/min,
•serious GI conditions (abnormalities of the esophagus
that delay emptying), or
•pregnant
•Drug interaction
•Because of poor bioavailability, oral bisphosphonates
should not be administered at the same time as other
medications.
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55. Cont.….
Dosing and administration
•Because bioavailability is very poor for bisphosphonates
(less than 1%) and to minimize GI side effects,
• each oral tablet should be taken with at least 180 ml of
plain water
•at least 30 minutes (60 minutes for ibandronate) before
consuming any food, supplements or medications
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56. Cont.….
•The patient should also remain upright for at least
30 minutes to1 hour after administration.
•For patients with swallowing difficulties (eg, stroke
and tube feeding), an effervescent tablet form of
alendronate, which is dissolved in 120 ml of room
temperature water, could be used
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57. cont.….
Duration
•The ideal duration is not known.
•They are deposited into the bone and continue to
suppress bone turnover after discontinuation.
•To balance risk and benefit, some clinicians
recommend a “bisphosphonate holiday,”
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58. cont.….
•defined as disruption of therapy during which
medication effects exist with a plan for medication
reinstitution.
•Experts recommend that a bisphosphonate
holiday could be considered in postmenopausal
women after 5 years of oral bisphosphonates or 3
years of intravenous bisphosphonates
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59. Alendronate • Treatment: 10 mg orally daily or 70 mg
orally weekly
• Prevention: 5 mg orally daily or 35 mg orally
weekly
Ibandronate • Treatment: 150 mg orally monthly, 3-mg
intravenous quarterly
• Prevention: 150 mg orally monthly
Risedronate • Treatment and prevention: 5 mg orally
daily, 35 mg orally weekly, 150 mg orally
monthly
Zoledronic
acid
• Treatment: 5-mg intravenous infusion
yearly
• Prevention: 5-mg intravenous infusion
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60. Cont.…
4. mixed estrogen agonist/antagonist (EAA)
•These are medicines that have a similar effect on
bone as the hormone estrogen. They help to
maintain bone density and reduce the risk of
fracture, particularly of the spine.
•Raloxifene
•the only type of EAA (A second-generation)
available for treating osteoporosis. It's only
recommended for women, after the menopause.
It's taken as a daily tablet.
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61. Cont.…
•Approved by the FDA for prevention and
treatment of postmenopausal osteoporosis and
for reducing the risk of invasive breast cancer in
postmenopausal women
•Raloxifene’s breast cancer–prevention benefits
make this medication desirable for younger
postmenopausal women at risk for or with
osteoporosis and breast cancer.
•Raloxifene is an agonist at bone receptors and
antagonist at breast receptors
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62. Cont.….
•Bazedoxifene
•A third-generation EAA combined with
conjugated equine estrogens (CEE) making it a
tissue selective estrogen complex (TSEC)
•Approved by FDA for prevention of
postmenopausal osteoporosis
•it is an agonist at bone, and antagonist at the
uterus and breast; however, it has no breast
cancer prevention effects.
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63. Cont.…
•Adverse events
•Hot flushes are common with raloxifene but
decreased with bazedoxifene with CEE
•Bazedoxifene with CEE also has all the adverse
effects listed for estrogens
•Dosing and administration
•are administered orally once daily
12/29/24 63

64. Raloxifene 60 mg daily
Bazedoxifene with
conjugated equine
estrogens (CEE)
20 mg plus 0.45 mg
CEE daily
12/29/24 64

65. Cont.….
5. Calcitonin
•Is a hormone made by thyroid gland makes
and releases to help regulate calcium levels in
blood by decreasing it.
•Calcitonin is FDA indicated for osteoporosis
treatment for women who are at least 5 years
past menopause.
12/29/24 65

66. Cont….
6. Parathyroid hormone analogue
•Produced naturally in the body. It regulates the
amount of calcium in bone.
•used to stimulate cells that create new bone. Can be
taken as an injection once a day.
•Abaloparatide and teriparatide
•These agents are fda indicated for the treatment of
postmenopausal women with osteoporosis at high
risk for fracture
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67. Cont….
• Defined as multiple risk factors for fracture, a history of
osteoporotic fracture, or failed or intolerant to other
therapies.
•Teriparatide is additionally fda indicated for men with
idiopathic or hypogonadal osteoporosis who are at high risk
for fracture, men intolerant to other osteoporosis
medications, and patients with glucocorticoid-induced
osteoporosis.
12/29/24 67

68. Teriparati
de
•20-mcg subcutaneously daily
for up to 2 years
Abalopara
tide
•80-mcg subcutaneously daily
for up to 2 years
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69. Questions
12/29/24 69

70. Osteoarthritis
(OA)
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71. Definition
•Degeneration of joint cartilage and the underlying
bone
• a vital tissue that enables smooth and efficient
joint movement by reducing friction and
absorbing shock
•progressive joint failure where all structures
involved in joint function undergo progressive
deterioration and loss of articular cartilage
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72. Cont….
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73. Joints affected by OA
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74. Etiology
•Primary (idiopathic)-- the most common
type, has no known cause.
•Localized (involving one or two sites)
•Generalized (affecting three or more
sites).
•Erosive the presence of erosion and
marked proliferation
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75. Cont.….
•Secondary-- associated with a known
cause such as
•Rheumatoid arthritis or another
inflammatory arthritis, trauma, and
congenital factors.
12/29/24 75

76. Cont.…
Risk factors
•Aging
•Obesity
•Repetitive use through work
•Joint trauma
•Heredity
12/29/24 76

77. Pathophysiology
•It usually begins with
•Damage to articular cartilage through
injury,
•Excess joint loading from obesity or other
reasons,
•Joint instability or injury that causes
abnormal loading.
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78. Cont…
•In response to cartilage damage,
chondrocyte activity increases in an attempt
to remove and repair the damage.
•Depending on the degree of damage, the
balance between breakdown and re-
synthesis of cartilage can be lost
•The increasing breakdown can lead to further
cartilage loss and apoptosis of chondrocytes
12/29/24 78

79. Cont.…
•Subchondral bone adjacent to articular
cartilage also undergoes pathologic
changes---new bone formation
•Loss of cartilage + new bone formation
causes joint space narrowing , painful, and
deformed joints.
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80. 12/29/24 80

81. Clinical presentation
•The prevalence and severity of OA
increase with age.
•Clinical presentation depends on duration
and severity of disease and the number of
joints affected.
•Localized deep pain associated with the
affected joint.
•At early stage pain decreases with rest.
12/29/24 81

82. Cont…
•Imitation of motion, stiffness, and
deformities.
•Joint stiffness typically lasts less than 30
minutes and resolves with motion.
•Warm, swollen, red, and tender joint.
•Physical examination of the affected joints
reveals tenderness and possible joint
enlargement.
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83. DIAGNOSIS
•Patient history, clinical examination radiologic
findings, and laboratory testing.
•Classification
•For hip OA , a patient must have hip pain and
two of the following:
•an ESR > 20 mm/hr
•radiographic femoral or acetabular
osteophytes
•radiographic joint space narrowing.
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84. Cont.…
•For knee OA , a patient must have knee pain
and radiographic osteophytes in addition to
one or more of the following:
•age greater than 50 years
•morning stiffness of 30 minutes
•bony enlargement and tenderness
•palpable joint warmth.
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85. Management
•Goals
•relieve pain and stiffness
• maintain or improve joint mobility
• limit functional impairment
• maintain or improve quality of life
•NB: treatment of OA may relieve pain or improve
function but does not reverse preexisting damage
to the joint.
12/29/24 85

86. CONT….
Non pharmacologic
•Educate the patient about the extent of the
disease, prognosis, and management approach.
•Dietary counseling and a structured weight-loss
program for overweight patients
•Physical therapy—with heat or cold treatments
and an exercise program
•To strengthen muscles, improve joint
function and motion, and decrease disability,
pain.
12/29/24 86

87. CONT….
•Assistive and orthotic devices such as
canes, walkers, braces, heel cups, and
insoles.
•Surgical procedures (e.g. Osteotomy, partial
or total arthroplasty, joint fusion)
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88. Cont.…
Pharmacologic
•Drug therapy in OA is targeted at relief of pain.
•Acetaminophen is recommended as first-line drug
therapy
•Application of topical NSAIDs over specific joints
(knee, hands) and topical capsaicin (hands) are can
be recommended as initial therapy
•NSAIDs at prescription strength are often
prescribed for OA if acetaminophen is ineffective, or
for patients with inflammatory OA.
12/29/24 88

89. Cont.…
•Topical therapies (capsaicin) causes release
and ultimately depletion of substance p from
nerve fibers and relief pain.
•Systemic corticosteroid therapy is not
recommended in OA , given the lack of
proven benefit and the well-known adverse
effects with long-term use
12/29/24 89

90. Cont.….
•Intra articular corticosteroid injections are
recommended as alternative first-line
treatment for both knee and hip OA
•When pain control with acetaminophen or
NSAIDs is suboptimal
•Should not be administered more frequently
than once every 3 months due to risks of
systemic adverse effects
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91. Cont.…
•tramadol is recommended as an alternative
first-line treatment in patients who have
failed treatment with
•scheduled full-dose acetaminophen and
topical NSAIDs
•are not appropriate candidates for oral
NSAIDs
•are not able to receive intra articular
corticosteroids.
12/29/24 91

92. Cont.…
•tramadol can also safely be added to
partially effective acetaminophen or oral
NSAIDs therapy.
•second line ---opioids
12/29/24 92

93. Treatment recommendations for knee and hip OA
12/29/24 93

94. Treatment recommendations for hand OA
12/29/24 94

95. Anti inflammatory pathway of NSAID, Corticosteroids
12/29/24 95

96. Algorithm for the use of long-term NSAID therapy
12/29/24 96

97. 12/29/24 97

98. Cont…
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99. Cont’d…
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100. Cont’d…
12/29/24 100

101. Cont.…
Evaluation of treatment outcome
•Monitor efficacy, by assessing level of pain, range of
motion.
•Monitor adverse effects of medications
• Baseline serum creatinine, hematology profiles, and
serum transaminases with repeat levels at 6-12 month
intervals.
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102. Questions
12/29/24 102