Bone loss occurs without symptoms and the first sign may be a fracture due to weakened bones caused by a sudden strain. Osteoporosis is characterized by compromised bone strength that increases the risk of fracture. While bone loss occurs without symptoms, the first sign is often a fracture that results from a minor strain or impact that would not normally cause a break in healthy bone.

1. .
Bone loss occurs without symtoms
First sign may be a fracture due to weakened bones
A sudden strain may lead to a fracture
Dr.sanam

2. OUTLINES
• Introduction
• Incidence
• Risk factors and types?
• Whom and how to evaluate?
• How to monitor? what is successful treatment? how long?
• Summarized algorithm of treatment guidelines
• Conclusion

3. • Osteoporosis is a
skeletal disorder
characterized by
compromised bone
strength predisposing
to an increased risk of
fracture.
• .

4. Normal has appearance of a honeycomb matrix
(left) .Under a microscope , osteoporotic bone
looks more porous.

5. Osteoporotic fractures account for 0.83% of global
burden of noncommunicable diseases.
• Patients may confuse osteoporosis with
degenerative conditions
• Acute pain in vertebral fracture usually
resolve in 4-6 weeks.

7. 0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,600,000
Breast
Cancer
Heart
Disease
Osteoporotic
Fractures
Cases/Year
Women’s Health Facts and Figures. Washington, DC: ACOG; 2000.
Contd.

8. NIH/ORBD National Resource Center. October 2000.
Wrist
16%
(250,000)
Hip
19%
(300,000)
Other
19%
(300,000)
•
Vertebral
46%
(700,000)
Clinical features & Consequences

9. Bone remodeling
Peak Bone Mass
Osteoblast Osteoclast
Aging
Altered
remodeling
Bone loss/
Osteoporosis/ Fracture
Nutrition: Ca, Vit
D, Calorie, Protein,
other minerals
Physical activity
Hormone
Chronic disease/
Disease favors bone
demineralization
Medications
Risk factors
Genetics: Race,
Family Hormone

13. Disease/ Conditions associated with
Osteoporosis: 2nd Osteoporosis
Hypogonadal states Endocrine disorders
Premature menopause Cushing’s syndrome
Turners syndrome Hyperparathyroidism
Klinefelter syndrome Hyperthyroidism (3 yrs)
Other primary/ secondary
hypogonadanadal states
Type 1 DM
Low estrogen >Amen> 6 months Adrenal insufficiency
Hyperprolactinemia GH deficiency
Anorexia nervosa Acromegaly with hypogonadism
Athletic amenorrhea

14. Nutrition & GI disorders RheumA/inflammatory conditions
Malnutrition, lactose intolerance RA
Prolonged parenteral nutrition Ankylosing spondylitis
Malabsorption syndrome: Coeliac, CD
Gastrectomy
Severe/ chronic liver disease

15. BLOOD disorders & malignancies Inherited disorders
Multiple myeloma Osteogenesis imperfecta
Leukemia Marfan syndrome
Paraneoplastic syndrome (PTHrP) Ehlers’s Danlos syndrome
Thalassemia
Hemophilia

16. Other disorders Drugs
Immobilization Systemic glucocorticoids GCs> 3m>
7.5 mg pred
COPD Cytotoxic drugs/ chemotherapy
Multiple sclerosis Cyclosporin
Sarcoidosis Anticonvulsants (long term)
Heparin long term
Excessive thyroxine

17. Whom and How to Evaluate
Osteoporosis

18. C `1
NationalOsteoporosis
Foundation
and
American College of
Preventive
Medicine
Postmenopausal women Age ≥ 65 years without
risk factors or ≤ 65 years
with risk factors
Men Age ≥ 70 years without
risk factors or < 70 years
with risk factors
Whom to evaluate?

19. North American
Menopause
Society
Postmenopausal women Age ≥ 65 years without
R.F or≤ 65 years with R.F
Postmenopausal women
with medical causes of
bone loss or fragility
fracture, regardless of
age

20. Osteoporosis
How to Evaluate
Clinical
History
Clinical
Examinations
Investigations

21. Clinical Presentations: History and physical
findings
• Usually asymptomatic unless fracture
• Doesn’t cause generalized skeletal pain
• Sudden localized pain with or withoutH/o injury
• Persistent back pain
• Height loss (.1 to 1.5 inch)
• Kyphosis
• Fragility fractures

22. Complications: Hip
• Pain,immobility
FRACTURE
DVT, Pul embolism
• Cause of death
Hip #: 5% to 20% during year of
surgery

23. Vertebra
• Long term morbidity
Multiple # > height loss, kyphosis,
Thoracic #: restrictive lung disease
Lumber #: abdominal distention,
early satiety, constipation.

24. Assess
• Risk factors
• Conditions/ diseases/ Medications associated
with 2nd Osteopororsis

25. Investigations

26. Two major tool
• BMD:
– Diagnosis/ Status
– Treatment decision
• FRAX Tool (WHO)
– Risk assessment
– Treatment decision
Dennis M, NEJM 2016.

27. Measures of Bone Mass (BMD)
• DEXA: Standard for
BMD
• Others
– SEXA
– CT–based
absorptiometry
• (quantitative CT),
– Quantitative
ultrasound
densitometry
WHO, NOF

28. Definition by DXA scoring
T score Category
> -1 Normal
< -1 to > 2.5 Osteopenia
<-2.5 Osteoporosis
<-2.5 with
fragility fracture
Established/severe
osteoporosis
WHO Criteria

29. 1.Risk factors are
combine with femur
neck BMD to calculate
10 year probability of #
and
2.FDA approve
treatment if hip #>3%
or MO#>20%

31. Most useful Others
CBC, ESR Oestradiol, FSH
LFT Serum & Urine electrophoresis
(BJP), Punch out lesion X rays
RFT Endomysial ab, TTG ab, biopsy
Calcium, P,albumin, alk Phos,
24 h U ca, PTH
U free cortisol, Overnight DST
Vitamin D Isotope bone scan
Thyroid function tests Albumin, cholesterol, Vit B12,
folate, iron profile
Testosterone, LH, SHBG
X-rays for evidence of previous
fractures/ fragility fracture
As appropriate for secondary
causes

32. Management aspect of
osteoporosis

33. • Prevent further bone loss
• Increase or at least stabilize bone density
• Prevent further fractures
• Relieve deformity (e.g., kyphoplasty)
• Relieve pain
• Increase level of physical functioning
• Increase quality of life
Goals of treatment

34. Lifestyle Advice
Diet Exercise
Smoking
Stop smoking
Stop Alcohol
Sunlight Exposure

35. Nonpharmacologic Measures in PMO
Treatment
35
• Maintain adequate protein intake
• Use proper body mechanics
• Consider use of hip protectors in individuals
with high fall risk
• Take measures to reduce fall risk
• Limit alcohol and caffiene intake.
• Consider referral to PT and OT

36. Who Needs Pharmacologic Therapy?
• H/o of a fragility # of hip or spine with osteopenia
• NO history of # but with a T-score of -2.5 or lower
• T-score b/W -1.0 and -2.5 if FRAX for 10 year major
osteoporosis related # probability at 20% or > or hip #
probability at 3% or >

37. Pharmacologic approaches to
osteoporosis
Antiresorptive agents
• Calcium
• Vitamin D and calcitriol
• Estrogen
• SERMs
• Calcitonin
• Bisphosphonates
• RANK-ligand inhibition
Bone-forming agents
• Androgens
• Parathyroid hormone

38. What Drugs Can Be Used to Treat PMO
38
Use Drugs with Proven Antifracture Efficacy
first line therapy
•alendronate, risedronate, zoledronic acid, and denosumab
Second line therapy
• Ibandronate
Third line therapy
• Raloxifene
Last line of therapy
• calcitonin
• Use teriparatide for patients with very high fracture risk or patients in whom
bisphosphonate therapy has failed
• Advise against the use of combination therapy
– Cost, improved efficacy not documented, safety

39. • Must be used with other treatment options
• A very good option to treatOsteopenia
• Insufficient to treat Osteoporosis
• Vitamin D
Measure 25-OH vitamin D in those at risk for insufficiency
Preferable range 25-OHD : 30 ng/ml to 50ng/ml
Supplementation if needed: generally in range of 600 to 800 IU daily with higher amounts in some
patients
• Calcium
Counsel on adequate dietary intake of calcium – about 1000 to1200 mg daily
39
Calcium & Vitamin D

40. 40

41. •Estrogen meets up the hormonal scarcity in postmenopausal women
• Elevates the calcium level in circulation
•Decreases bone resorption
41
Estrogen

42. • Raloxifene,Selective estrogen receptor modulator has been used to treat
Osteoporosis.
• Estrogen agonist activity in some tissues and antagonist in other tissues.
• Introduced to overcome the side effects of ERT/HRT.
• Not a very good option for Severe Osteoporosis & Osteoporotic pain.
42
SERM

43. • A good option to treat PostmenopausalOsteoporosis
• Very effective to control Osteoporotic Pain
• Can reduce vertebral fracture rate
• Convenient treatment option
• Difficult to treat severe Osteoporotic patients
43
Calcitonin

44. Effects of Bisphosphonates on Osteoclast Function
Normal Osteoclast
Cytoskeletal
disorganization1
Altered vesicular
trafficking3
Loss of ruffled
border1
Cell death by apoptosis2
1. Sato, M, et al. J Clin Invest. 1991;88:2095-2105. 2.
2. Hughes DE, et al. J Bone Miner Res. 1995;10:1478-1487.
3. Rogers M. Curr Pharm Des. 2003;9:2643-2658.
44

46. Bisphosphonate- side effects
• Low bioavailability in contrast to IV, poor
compliance with oral BP
• Having chance of GERD, PUD with oral BP.
• Other side effects are common for all BP - atypical
•fracture of femur, ONJ, AF, esophageal cancer
The Journal of Family Medicine June2010;59:200-6

47. • Although IV BPs are generally safe, transient influenza-like
symptoms.
• ONJ- 1-19 per 100,000 (IV: oral = 3:1).
• Upto 18.6% in oncology patients
• Atypical # of femur with bisphosphonate for as long as
10 years – large studies – FIT 1996, FLEX 2016, HORIZON 2007
did not support
Contd….
N Engl J Med 2010:1761-71
PEOPLE AT RISK FOR ONJ
• Cancer & anti-cancer therapy
• Dental extraction, oral bone manipulating surgery
• Poor fitting dental appliances
• Intraoral trauma
• Duration of exposure to bisphosphonate treatment
• Comorbidity- malignancy,alcohol abuse, use of tobacco
• Periodontal disease

48. PTH and Teriparatide
o PTH 1-34 (teriparatide) and PTH 1-84, anabolic drug
o Not beyond 2 years.
o Highest BMD achievement & reduction of vertebral
o fracture - Add on therapy.
o Dose: 20 mcg per day SC for 2 years.
o One study suggests that it is advisable to follow teriparatide therapy with
bisphosphonate therapy to maintain BMD gains.
o Side effects-
o Orthostatic hypotension, nausea, myalgia, and
oarthralgia, risk of osteosarcoma

49. Who Should Not be Considered for Teriparatide
Therapy?
• Hypercalcemia
• Paget’s disease
• Osteogenic sarcoma
• Unfused epiphysis
• Previous irradiation to the skeleton
• Pregnancy or breast-feeding
• Bone cancer or metastatic cancer to bone
• Allergic reaction to PTH or to ingredients in the vehicle

50. Denosumab
A anti-resorptive therapy.
Monoclonal antibody against RANK ligand.
Approved for postmenopausal osteoporosis in USA.
Dose- 60mg s/c injection every 6 month for 3 years
Combined denosumab & teriparatide achieves improved BMD
response vs either agent alone but data for # risk are lacking.

51. How is
Treatment Monitored?
• Obtain a baseline DXA, and repeat DXA every 1-2 years until
stable. Continue follow-up every 2 years or at a less frequent
interval
• Monitor changes in spine or total hip BMD
• Follow-up same facility, same machine, and if possible, the
same technologist

52. What is Successful Treatment of Osteoporosis?
• BMD is stable or increasing and no fractures are present
• For patients taking antiresorptive agents, bone turnover
markers at or below the median value for premenopausal
women are achieved
• One fracture is not necessarily evidence of failure.
• Consider alternative therapy or reassessment for secondary
causes of bone loss for patients who have recurrent fracture
while receiving therapy

53. How long ?
• Teriparatide –limited to 2 yrs
• For oral bisphosphonates, consider a “bisphosphonate holiday” after 5
yrs of stability in moderate-risk pts .
• For oral bisphosphonates, consider a “bisphosphonate holiday” after 6 to
10 years of stability in higher-risk pts
• For I/V zoledronic acid, consider a drug holiday after 3 annual doses in
moderate-risk pts and after 6 annual doses in higher-risk pts.
• Teriparatide or raloxifene may be used during “bisphosphonate
holiday” period for higher-risk pts.

54. Drug holiday
• A drug “holiday” is not recommended withdenosumab
• The ending of “holiday” for bisphosphonate treatment should
be based on individual patient circumstances (fracture risk or
change in BMD)
• Other therapeutic agents should be continued for as long
as clinically appropriate

55. When Should Patients Be Referred to
Clinical Endocrinologists?
55
• When a patient with normal BMD sustains a fracture without
major trauma
• When recurrent fractures or continued bone loss occurs in a
patient receiving therapy without obvious treatable causes of
bone loss
• When osteoporosis is unexpectedly severe or has unusual
features
• When a patient has a condition that complicates management
(for example: renal failure, hyperparathyroidism,
malabsorption)

57. ??
The present ACR guideline outlines the treatment recommendations for GIOP. The guideline
was developed to included therapies for the treatment of OP approved by the US Food and
Drug Administration before 2015.
Glucocorticoid induced osteoporosis

58. Clinical factors that may shift an individual to a greater risk
category for glucocorticoid-induced osteoporosis
• Low body mass index
• Parental history of hip fracture
• Current smoking
• ≥3 alcoholic drinks per day
• Higher daily glucocorticoid dose
• Higher cumulative glucocorticoid dose
• Intravenous pulse glucocorticoid usage
• Declining central bone mineral density measurement that exceeds the
least significant change

61. Novel & Future Therapies- new armaments
• Monoclonal antibody Sclerostin antagonist –
Romosozumab.
• PTH & PTHrp analogues, possibly calcilytics-
JTT305/MK-5442
• Inhibitors of bone resorption as Cathepsin K inhibitors-
Odanacatib
• Sequential therapies with 2 or more bone active
substances.

62. Challenges & controversies still we need to face
• Impact of osteoporosis is high.
• Underlying pathology – still in innovation.
• Racial variation of peak bone mass not known.
• DEXA measurement is not available everywhere.
• Expensive drugs.
• No pharmacologic agent can effectively increase both
non-spine and spine BMD.

63. Conclusion
• OP is under recognized & treated in PMO & elders
• Diagnostic Tools would be ( BMD & FRAX)
• Non Pharmacologic therapy- Vit D & Ca supplementations
• Pain management with analgesic ladder, physical therapy , surgery.
• Currently approved drugs are SERM, Calcitonin, PTH, Bisphosphonate,
Denosumab.
• BP is foundation of therapy
• Newer drugs - Cathepcin K inhibitor-Odanacetib,
oral PTH, oral Calcitonin, Romosozumab.