No

1. SECONDARY OSTEOPOROSIS
-
A PRACTICAL APPROACH
Dr. Niti Dogra
M.S.(OBS & Gynae)

2. What is SECONDARY OSTEOPOROSIS?
• SECONDARY OSTEOPOROSIS is loss of Bone or
Alteration in the Bone Microstructure and Occurrence
of Fragility Fractures due to Underlying Disease or
Medication.

3. • 20 to 30% of Post Menopausal women and 50% of
Men with Osteoporosis have one or more Secondary
Contributors.
• It is quite common in Pre-Menopausal women (50%)
• In a study conducted in India, it was found that almost
half of the Patients with Osteoporosis have One or
More Secondary Cause.
Why is it important?

4. DISEASE BURDEN
• Mortality from a HIP Fracture – 5 to 20 %
• Morbidity ( Requiring Long Term Care) – 30%

5. • WHO Defines Osteoporosis as a Bone Density that
falls 2.5 Standard Deviation below the Mean for
Young Healthy Adults of Same Sex and Race, also
referred to as a T SCORE of -2.5.
WHO definition of Osteoporosis.

6. • Z – Score is the number of SDs by which the BMD
is an individual differs from the main value expected
for the Age and sex.
• A Z - Score below -2 is considered abnormal and
should be referred to as low for age
• A low Z – Score indicates the need to evaluate for
secondary osteoporosis.
What is a Z-Score?

7. • Osteoporotic related Fractures are Adulthood Fractures
of any Bone that Occur in the setting of Trauma less
than or equal to a Fall from Standing height
• With the Exception of :
• Skull
• Face
• Toes
What is Osteoporotic related fracture?

8. • During Later in Life, Bone remodelling (Resorption &
Formation) becomes Imbalanced, specially in Women
after Menopause
• This Leads to:
• Increased Osteoclastic Activity
• Decreased Osteoblastic Activity
• Increase in Bone Remodelling also lead to Permanent
Loss of Tissue and Disrupted Skeletal Architecture
Pathophysiology

9. BONE REMODELING CYCLE

10. CAUSES OF SECONDARY OSTEOPOROSIS
1. Endocrinal causes
2. Medications
3. Malabsorption syndrome
4. Dietary causes & smoking
5. Decreased physical activity
6. Systemic diseases
7. Haematological disorders
8. Inherited disorders

11. ENDOCRINAL CAUSES
• Diabetes
• Thyrotoxicosis
• Hyperparathyroidsm
• Cushing’s syndrome
• Adrenal insufficiency

12. MEDICATIONS
• Glucorticoids
• Anticonvulsants – phenytion, vaproic acid,
carbmazepine
• Ppi
• Oha - glitazones
• Loop diuretics
• Heparin
• Ssris

13. • Lithium, aluminium containing medicines
• Cytotoxic and immunosuppressive agents
• Dmpa
• Gnrh Agonists
• Att
• Orlistat

14. DIETARY CAUSES
• Aromatase inhibitors
• Vitamin-D deficiency
• Excessive protein intake
• Increased Vitamin-A intake
• Smoking and alcohol
• Parenteral nutrition
• Anorexia nervosa

15. HAEMATOLOGICAL DISORDERS
• Thalassemia
• Multiple myeloma
• Lymphoma and leukaemia
• Haemophillia
• [Increased bone turn over states]

16. NUTRITIONAL DISORDERS
• Protein energy Malnutrion
• Liver diseases (biliary cirrohosis)
• Pernicious Anaemia
• Post Gastrostomy status
• Bariatric surgery

17. Rheumatologic disorders
•Rheumatic arthiritis
•Ankylosing spondilitis

18. Inherited causes
• Osteogenesis imperfecta
• Marfan syndrome
• Hemochromatosis
• Glycogen storage diorders
• Ehler danlos syndrome

19. Other diseases
• Immobilisation
• Pregnancy and lactation
• Scoliosis
• Copd
• Multiple sclerosis
• Sarcoidosis

20. GLUCOCORTICOIDS AND OSTEOPOROSIS-
most important single cause for secondary osteoporosis
• Glucocorticoids are widely used now days for a variety
of disorders :
• COPD
• RA
• Connective Tissue Disorders
• Inflammatory Bowel Disease
• Post Transplant Cases
NO SAFE DOSE
NO SAFE DOSE

21. • Osteoporosis Related Fractures are Serious Side
Effects of Chronic Steroid Therapy
• Rate of Bone loss due to Steroid Therapy is
approximately 10- 20% per year compared to bone
loss post Menopause which is 1-2% per year
• Risk of Fracture is directly proportional to the Dose
and Duration of Steroid Therapy

22. GLUCOCORTICOIDS AND OSTEOPOROSIS (CONTINUED)…
• Bone Loss is More Rapid in Early Months Of
Treatment
• Trabecular Bone is More commonly Affected
• There is an Increase in Fracture Risk within 3 months
of Starting Steroid Treatment
• All routes of Steroids are considered dangerous
including Intra-Articular and Inhalation.

23. Steroid effects on bone
• Altered Osteoclast Function
• Increase Osteoblast Apoptosis
• Increase Bone Resorption
• Decrease Calcium Absorption from Intestine
• Increase Calcium Loss from Urine
• Decrease Adrenal Androgens and suppress secretion of
Testicular and Ovarian Hormones

24. • Steroid Induced Myopathy also leads to Increase
tendency to fall, leading to Fracture of already
weakened Bones.

25. GLUCOCORTICOIDS AND OSTEOPOROSIS (CONTINUED)
Assess the Skeleton of all people on Chronic Steroid
Intake
Height
Muscle Strength
24 hr. Urinary Calcium
DXA Scan – Both Hip & Vertebrae
If ONE Site - Spine for people less than 60 yrs.
- Hip for People more than 60 yrs.

26. TREATMENT OF GLUCOCORTICOID INDUCED
OSTEOPOROSIS
• Bisphosphonates
• Teriparatide
• Denosumab

27. ESTROGENS & OSTEOPOROSIS
Estrogens have PROTECTIVE Effects on Bon
ESTROGEN DEFICIENCY LEADS TO:
• Increase in Apoptosis Of Bone cells
• Decreased Osteoblastic Life Span
• Increase Osteoclastic Formation

28. • Increased Activation of New Bone Remodelling
Sites - Increased Osteoclastic invasion of
Trabeculae, leading to a permanent loss of template
for new bone formation – Rapid bone loss ensues.
• Exaggeration of Imbalance between Bone Formation
and Bone loss

29. DIABETES & OSTEOPOROSIS
• Diabetes causes an alteration in Chemical
composition of Bone Tissue making it more brittle.
• Diabetes increases conversion of Precurssor Cells
of Osteoblasts into Adipose Tissue
• Diabetes increases Neuropathy and Myopathy,
leading to increased propensity to fall–causing
Fractures.

30. WHEN IS BMD INDICATED?
• Adults with fracture at 50 years or above
• Young post menopausal women
• Women > 65 regardless of clinical
• Men > 70 risk
• Men 50-69 years with clinical risk for fracture.
• In pre – menopausal women when :–
• Secondary cause is there

31. • Presence of VCF
• History of fragility fractures
• Pit fall of BMD does not give insight about the
skeletal architecture of the bone.
• Is it Under used ?

32. SMOKING
• Direct toxic effect on osteoblast
• Modifies estrogen metabolism
EXERCISE
• Reduces Bone Loss
• Improves Neuromuscular Function
• Improves Coordination
• Improves Balance
• Increases Muscle and Bone Strength
• Reduces the Risk of Falls
• However, the beneficial effects wane off once we discontinue
exercise

33. VITAMIN-D DEFICIENCY
• Most common causes of the Vitamin-D deficiency -:
• Poor nutrition
• Malabsorption
• Liver and kidney disease
• Obesity (volumetric dilution into the greater volumes of
fat , serum , liver , and muscle.)
• Inadequate sunlight
• Use of sunscreen
• Vit-D PTH
• ALP
• ionic Ca

34. VITAMIN-D
(multi-plural hormone)
DIABITES
ANTI-
AGEING
ABDOMINAL
OBESITY
DEPRESSION
AND OTHER
MENTAL
PROBLEMS
CARDIOVASCULAR
PROBLEMS
HYPERTENSION
INFERTILITY

35. CAREFUL HISTORY & EXAMINATION TO
IDENTIFY RISK FACTORS
• H/o Fall
• H/o Fracture after trivial Trauma
• H/o Any of the above mentioned Diseases and
Malignancy
• Medication History
• H/o Smoking and Alcohol
• H/o abdominal symptoms and Backache
• H/o Groin Pain ( Predictive Fracture indicator)

36. CAREFUL HISTORY & EXAMINATION TO
IDENTIFY RISK FACTORS ( CONTINUED)
• Height Loss greater than 1 – 1.5 inches ( R/o Vertebral
fracture)
• Look for Features for Insulin Resistance
• Look for Cushingoid features

37. INVESTIGATIONS
• CBC
• Blood Sugars ( HBA1C )
• TSH, Fasting sreum Phosphorous
• LFT
• RFT
• Serum & Urinary Calcium
• Urinary Calcium less that 50 mg in 24 hrs –
Malnutrition or malabsorption

38. • Urinary Calcium more than 300 mg in 24 hrs –
Hypercalciuria
• ( Exclude Calcium supplements 1 week before test)
• Serum Cortisol Levels ( Fasting State)
• Alkaline Phosphatase Levels and Vitamin D levels
• DXA Scan, Xray of Thoraco-Lumbar Spine
• Bone Turnover markers (Osteoblastic - Osteocalcin,
Serum Peptide of type 1 collagen )
• Osteoclastic – Urine and Serum Cross linked N –
Telopeptide &C- Telopeptide )

39. NUTRITIONAL RECOMMENDATIONS
• CALCIUM :
• Children: ( 9 to 18 ) – 1300 mg/day
• Adults : ( 19-50 ) – 1000 mg/day
• 51 + - 1200 mg/day
• Best Sources: Dairy, Vegetables ( Broccoli, Kale )
Dried Figs
• Not more than 600 mg of Elemental Calcium per
dose

40. COMPARISON OF CALCIUM CONTENT OF
VARIOUS SUPPLEMENTS
CALCIUM
(1500)
ELEMENTAL
CALCIUM (%)
ELEMENTAL
CALCIUM (mg)
ABSORBED
CALCIUM (%)
ABSORBED
CALCIUM (mg)
Carbonate 40 600 26 156
Citrate 21 315 22 69
Lactate 13 195 32 52
Gulconate 9 135 34 45
Source : Levinson DI, Bockman RS. A review of calcium
preparations. Nutr Rev. 1994; (7) : 221-232.

41. NUTRITIONAL RECOMMENDATIONS
• Vitamin D : Sources: Milk, Egg Yolk, Salmon, fortified
soy milk, mushrooms, sunshine
• Target Level – More than 30 ng/ml
• Deficiency – Less than 20 ng/ ml
• RDA: (National Academy of Medicine)
• Less than 70 Yrs – 600 IU/day
70 yrs + - 800 IU/day

42. • In case of Osteoporosis: 1000 to 2000 IU /day
• Treatment of Vitamin D Deficiency:
• 50,000 IU/week for 3 to 12 weeks, followed
by maintainence therapy of 800 IU/day

43. TREATMENT
• HRT
• Estrogens
• Estrogens & Progesterone
• Women on Estrogen replacement have a 50%
reduction of Osteoporosis Related Fracture
• Benefit is Greatest if treatment is started early and
continued.

44. TREATMENT
SERMS
• Raloxifine – FDA Approved for Osteoporosis and Breast
Cancer
• Dose : 60mg/day
• Reduces Vertebral Fractures by 30-50%
• NO Effect On HEART
• NO Increase in Uterine Cancer

45. • Reduces LDL, Reduces Lipoprotein a, Reduces
Fibrinogen
• Increases HOT FLUSHES
• Increases DVT Risk
• Not to be given over 70 years of age

46. TREATMENT
SERMS ( Continued )
Bazodoxiphene – Marketed in combination with conjugated
estrogen for treatment of menopausal symptoms and
prevention of bone loss. It protects the Uterus and Breast
from effects of Estrogens and makes use of Progestins
unnecessary
Mode of Action Of SERMS : SERMS Bind to ER and
produce unique Receptor Drug Conformation, resulting
in differential effects on gene Transcription

47. TREATMENT
Bisphosphonates
Aledronate
Risedronate
Ibandronate
Zoledronic Acid
ARZ – Treatment of osteoporosis in Men and in
Steroid Induced Osteoporosis
Z – Prevention of Steroid Induces Osteoporosis

48. TREATMENT
Alendronate :
• 5 mg/day for Prevention
• 10 mg/day for Treatment
• Usually give as 70 mg/wk ( Improves Compliance,
reduces GI Effects)

49. Risedronate :
• 35 mg / wk
• Ibandronate:
• 2.5 mg/day
• 150 mg/month orally (better Results)
• 3 mg IV every 3 months
Zoledronic Acid :
• 5 mg over 15 minutes IV once a year

50. TREATMENT
Bisphosphonates
• Mechanism of Action:
• Bisphosphonates are structurally related to
Pyrophosphates, compounds that are incorporated into
Bone Matrix.
• They Reduce Osteoclast Function and Number
( Increase Apoptosis)

51. Side Effects:
• Musculoskeletal and Joint Pains
• Osteonecrosis of Jaw
• Atypical Femoral Fracture ( occur in Subtrochantric
femoral Region or Across the femoral Shaft distal to
lesser Trochanter)
• Potential for Renal toxicity ( Contraindicated with GFR
less than 35ml/min)

52. TREATMENT
Calcitonin
• It is a Polypeptide Hormone produced by Thyroid Gland
• Used in cases of:
• Paget’s Disease
• Hypercalcemia
• Osteoporosis in women more than 5 years after Menopause
• For Treatment : 200 IU /day Nasal Spray
• Not indicated in prevention of OSTEOPOROSIS
• Calcitonin Reduces Osteoclastic activity by direct Action on
the Osteoclast calcitonin Receptor

53. TREATMENT
Denosumab
• It is a fully Human Monoclonal Antibody to RANK L –
final common effector for Osteoclast formation, Activity
and Survival
• Potent Antiresorptive Action
• It is given twice yearly by Subcutaneous Injection – 60mg
in PFS (1ml)
• It also Reduces risk of Breast Cancer recurrence.

54. Side Effects:
• Atypical Fracture Femur
• Hypersensitivity
• Skin Rash, Eczema
• Hypocalcemia
• Rebound Increase in Bone Turnover once
treatment is discontinued, leading to Increased Bone
loss and Fracture risk.

55. TREATMENT
Parathormone:
• It is a polypeptide hormone.
• Although Increasd PTH causes Bone Loss, it can also exert Anabolic
Effects on Bone.
• Mild endogenous Hyperparathyroidism is associated with maintainence
of Trabecular Bone Mass.
• Exogenously administered PTH appears to have direct action on
Osteoblast activity, causing a true Increase in Bone Tissue and
restoration of Bone Microarchitecture.
• 20 microgram PTH daily by s/c injection reduces Vertebral fractures
by 65% and Non Vertebral Fractures by 40-50%

56. TREATMENT
Teriparatide
• It is a Recombinant fragment of Human Parathyroid
Hormone
• (Manufactured using a strain of E.Coli)
• Direct Osteoblastic Activity
• Increases Bone Formation
• Increases Bone Mass
• Improves Microarchitecture

57. • Increases Cancellous and Cortical Bone width
• Dose: 20 microgram/day subcutaneous (stored
between 2-8 C )
• Maximum Duration of Treatment– 2 years during a
patient’s lifeti
• Side Effects – Muscle Pain, Weakness, Dizziness,
Headache, Nausea, Hypercalcemia, Osteosarcoma

58. TREATMENT
Abaloparatide
• It is a Synthetic Analogue of Human PTH Related
Peptide.
• Slightly different Action profile compared to
Teriparatide
• Similar Bone formation but lesser Bone Resorption
stimulus ( thus more potent)
• Dose – 80 micrograms per day s/c

59. TREATMENT
Romosozumab
• It is a Humanized Antibody that blocks the production of
Sclerostin by Osteocytes, resulting in Reduced Bone
Resorption and Increased Bone Formation.
• Produced in a mammalian cell line
Dose – 210 mg s/c once a month for 12 months
Side effects – Rash, fever, gum swelling, muscle spasms,
joint pains

60. ENJOY
HEALTHY
AND
GRACEFUL
AGING
THANK YOU !