This document provides an introduction and overview of osteoporosis, including its definition, risk factors, diagnosis, and treatment. It begins with defining osteoporosis as a systemic skeletal disease characterized by low bone mass and deterioration of bone tissue, leading to increased bone fragility and fracture risk. It then discusses the main and other risk factors, methods of diagnosis including laboratory tests and DEXA scans, pharmacological treatment options including bisphosphonates, denosumab, teriparatide, and hormone therapies, as well as prevention strategies. The document concludes with several case studies examples to demonstrate treatment approaches.

1. Dr. Sameh Ahmad Muhamad abdelghany
Lecturer of Clinical Pharmacology
Mansura Faculty of medicine

2. 2
PROSIS
INTRODUCTION
RISK FACTORS
Diagnosis
Treatment & Prevention
Cases
CONTENTS

3. INTRODUCTION

4. 4
Introduction
 Definition:
 “systemic skeletal disease characterized by
low bone mass and microarchitectural
deterioration of bone tissue, leading to
enhanced bone fragility and a consequent
increase in fracture risk”
 True Definition: bone with lower density and
higher fracture risk
 WHO: utilizes Bone Mineral Density as
definition (T score <-2.5); surrogate marker

5. 5
Introduction
 Osteoporosis is common
 Over 50% of women and 30-45% of men
over age 50 have osteopenia/osteoporosis
 White woman over age 50: 50 % lifetime
risk of osteoporotic fracture, 25% risk
vertebral fracture, 15% risk of hip fracture
 Man over age 60 has 25% risk osteoporotic
fracture
 70% over age 80 have osteoporosis
 The word "osteoporosis" is from the Greek
terms for "porous bones".

6. RISK FACTORS

7. 7
Risk Factors
I. Main
 Age (increasing)
 Low BMI (small, low weight;< 58
kg)
 Ethnicity: Caucasian > Asian/Latino
> African American
 Family History of Fracture

8. 8
Risk Factors
II. Others
 Sex Hormones (low
estrogen/testosterone)
 Low calcium and vitamin D
 Inactive lifestyle
 Excessive alcohol
 Cigarette smoking

9. 9
Risk Factors
II. Others
 Hyperparathyroidism (primary or
secondary)
 Hyperthyroidism
 GI conditions which impair adequate
nutrition
 Steroids or Cushing’s
 Proton pump inhibitors

10. 10
Risk Factors

11. DIAGNOSIS

12. 12
Clinical Manifestations
 Generally patients are asymptomatic
even with very low bone densities
 Hip Fractures
 Acute or chronic back pain secondary
to vertebral fractures
 Atraumatic or low impact fractures

13. 13
Clinical Manifestations

14. 14
Clinical Manifestations

15. 15
Clinical Manifestations

16. 16
Laboratory diagnosis
 CMP (creatinine, calcium, alkaline
phosphatase)
 Creatinine: assess for renal function for
choice of treatment
 Calcium:
o if too low consider cause and replete
o If too high consider hyperparathyroidism
 Alkaline phosphatase: osteomalacia or
Paget’s disease

17. 17
Laboratory diagnosis
 25-OH Vitamin D
 Important to replete if low (low vit D can
lead to elevated PTH)
 24-hour Urine calcium
 Hypercalciuria: if elevated
 Malabsorption: if low

18. 18
Laboratory diagnosis
 PTH (with calcium)
 If calcium is elevated
 If considering using teriparatide
 Patients with ESRD
 Testosterone
 In men with osteoporosis
 24 hour urine cortisol
 In patients with cushingoid features and
unexpected osteoporosis

19. 19
Laboratory diagnosis
 DEXA scan
 Dual energy x-ray absorptiometry
 Measures bone mineral density,
approximation of bone mass and best
predictor of fracture risk
 Measurement: standard deviation of
normal young subjects (T-score) and age-
matched (Z-score)

20. 20
Laboratory diagnosis
 DEXA scan
 Uses
 To detect those at risk for bone fracture
 To confirm diagnosis of osteoporosis in
those with fracture
 To determine rate of bone loss
 To determine response to therapy

21. 21
Laboratory diagnosis

22. 22
T-score and Z-score
 T-score
 Postmenopausal women and men
 Used to determine if patient has osteoporosis
and whether treatment is required
 Z-score
 Premenopausal women
 Used to determine bone mineral density
relative to healthy young controls.
 For same score, risk of fracture is much lower
due to age.

23. 23
Bone Matrix Density(BMD)
 WHO: Osteoporosis: T score <-2.5
 Osteopenia: T score -1 - -2.5

24. TREATMENT

25. 25
Outcome Management
 Goals
 Treat Bone matrix density
 Prevent fracture

26. 26
Management
 Pharmacological
 Calcium and vitamin D
 Bisphosphonates
 Denosumab
 Teriparatide
 SERMs (Selective estrogen receptor
modulators)
 Hormone replacement therapy
 Calcitonin : no longer used

27. 27
Management
 Pharmacological
 Calcium and vitamin D
 Fewer than half adults take recommended
amounts
 Higher risk: malabsorption, renal disease,
liver disease
 Calcium and vit D supplementation
shown to decrease risk of hip fracture in
older adults

28. 28
Management
 Pharmacological
 Bisphosphonates
 generally 1st line
 E.g Medications: alendronate,
risendronate, zolendronic acid,
ibandronate.
 Suppress resorption by preventing
osteoclast attachment to bone matrix
 Cannot be used with eGFR < 30-35%

29. 29
Management
 Pharmacological
 Bisphosphonates
 Reduction in fracture risk by
approximately 50%
 Side effects:
o Esophagitis (not in IV forms)
o Osteonecrosis of Jaw
o Atypical fragility fractures, delayed
fracture healing

30. 30
Management
 Pharmacological
 Denosumab
 Shorter biologic half-life than
bisphosphonates
 Reduces Fractures
o vertebral by 68%
o Hip by 40%
 Approved for women receiving aromatase
inhibitors and men receiving gonadotropin
reducing treatment

31. 31
Management
 Pharmacological
 Denosumab
 Potential Adverse Effects
o Atypical fragility fractures
o Osteonecrosis of Jaw
o Possible increased risk of infections
o delayed fracture healing
 Contraindications:
o current hypocalcemia
o Pregnancy
o hypersensitivity

32. 32
Management
 Pharmacological
 SERM
 Selective Estrogen Receptor Molecules:
mixed agonists and antagonists of specific
estrogen receptors.
 Raloxifene:
o Decrease vertebral fracture by 55% (only
30% in those with history of vertebral
fracture)
o no effect on non-vertebral fractures

33. 33
Management
 Pharmacological
 SERM
 Decreases risk for breast cancer
 Adverse effects:
o Risk for CAD
o Venous thrombosis – increased risk
o Hot flashes and leg cramps

34. 34
Management
 Pharmacological
 Hormone Replacement Therapy(HRT)
 Estrogens +/- progesterones
 HRT was once considered to be the
primary therapy of osteoporosis
prevention/treatment
 Blocks cytokine signaling to the osteoclast

35. 35
Management
 Pharmacological
 Hormone Replacement Therapy(HRT)
 Women’s Health Initiative trial: 34%
reduction of hip fracture and vertebral
fractures, but increased risk for breast
cancer, cardiovascular disease, thrombosis
 Currently, HRT is not used to treat or
prevent osteoporosis alone (often used for
other indications such as severe
postmenopausal symptoms.

36. 36
Management
 Pharmacological
 Teriparatide
 Stimulates bone remodeling by increasing
bone formation
 Moderate to severe osteoporosis:
 Reduction of fractures:
o Vertebral : 65%
o Nonvertebral 53%

37. 37
Management
 Pharmacological
 Teriparatide
 High doses in rats caused osteosarcoma
but no cases of osteosarcoma seen in
patients who received the drug
 Should not be given for more than 2 years
 Side effects:
o mild hypercalcemia
 Expensive and subcutaneous
administration.

38. 38
Management
 Pharmacological
 Teriparatide
 Should not be given to patients with:
o Hypercalcemia
o Multiple Myeloma, bone mets, skeletal
tumor
o Children/teenagers with growing bones

39. 39
Prevention
 Adequate nutrition, particularly calcium
and vitamin D
 Calcium: 1000 – 1200 mg daily (diet
plus supplementation)
 Vitamin D: goal level of around 30-50
(most 1000 units daily)
 Weight bearing exercise

40. 40
Prevention
 Discourage smoking
 Discourage alcohol abuse
 Reduction of risks for falling: consider
evaluation for home hazards, minimize
sedating medications.
 Hip protectors: can be useful if worn
properly but often have low compliance.

41. CASES

42. 42
CASES
 CASE 1
 39 year old premenopausal female with
history of lupus who has been on long courses
of steroids and has had hip fracture after fall
from standing position a year ago. She has
chronically been on PPI for GI prophylaxis.
 She does not have family history of
fracture/osteoporosis, rheumatoid arthritis,
tobacco or alcohol.

43. 43
CASES
 CASE 1
 Labs: creatinine 0.9, Calcium normal, 25-OH
Vit D 15
 DEXA scan with Z score of -3.5 at spine and -
3.3 at hip.
 What are the next steps?

44. 44
CASES
 CASE 1
 Answer
 Replace Vitamin D
o 50,000 units weekly for 8-12 weeks, then
1000-2000 units/day
 Advise Calcium 1000-1400 mg daily
(supplement + diet)
 Teriparatide may be used as initial treatment
to increase bone density given several
fractures

45. 45
CASES
 CASE 2
 75 year old female with multiple myeloma
who has had multiple compression fractures
and was on alendronate for 5 years, then off
for 3 years; she had a hip fracture 10 months
ago.
 She has family history of fracture and bone
density shows decline in T score compared to
prior 2 years ago.

46. 46
CASES
 CASE 2
 DEXA scan with T-score of -3.6 at lumbar
spine and -2.9 at femoral neck.
 Creatinine 0.7, 25-Vit D 55, calcium normal,
PTH normal
 What is the next step?

47. 47
CASES
 CASE 2
 Answer
 Restart osteoporosis treatment with
denosumab (Prolia) since the patient is having
ongoing fractures and has decreasing bone
density.
 Avoid Teriparatide given diagnosis of multiple
myeloma.

48. 48
CASES
 CASE 3
 80 year old male with end stage kidney
disease with osteoporosis with T score of -3.1
at lumbar spine and -2.9 at femoral neck.
 He has kyphosis with vertebral compression
fractures on x-ray of thoracic spine.
 Estimated GFR 20, 25-OH-Vit D 40, calcium
normal, PTH mildly elevated.
 What is the treatment choice?

49. 49
CASES
 CASE 3
 Answer
 Denosumab (Prolia)
 Cannot use bisphosphonates given low eGFR.
 Avoid Teriparatide given elevated PTH
 For men, in general would be worth to check
testosterone level and consider replacement
therapy.

50. 50
CASES
 CASE 3
 70 year old female with osteoporosis with T
score of -2.1 at lumbar spine and -2.6 at femoral
neck.
 She has not had any fractures and does not have
any other risk factors; no history of tumors.
 She does have frequent falls
 FRAX with 10 year hip fracture risk of 3.6%
 Labs with creatinine 0.9, vitamin D 8, normal
calcium, elevated PTH
 What is the treatment?

51. 51
CASES
 CASE 3
 Answer
 Replete vitamin D since it is low
 Elevated PTH is likely secondary to low
vitamin D level
 Bisphosphonates would generally be
treatment of choice in this case.

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thanksF o r W a t c h i n g