Mapping the role of nutrition in

Osteoporosis
Sahara Star, Mumbai
 Group Members
Moderator -
Dr. Sushrut Babhulkar
Panelists
• Dr. Shivashankar Bhaskaran Pillai
• Dr. Swarnendu Samanta
• Dr. Rajeev Anand
• Dr. Anish Kumar Aggarwal
• Dr. Sameer Mehta
• Dr. Harmesh Kapoor
• Dr. Naresh Shetty
• Dr. Nallamilli Somasekhara Reddy
• Dr. Vikas Jain
• Dr. Jethwa Jawahar
• Dr. Akash Saraogi
• Dr. Ameet Pispati
• Dr. Rajesh Gandhi
• Dr. Ashok Shyam
• Dr. D D Tanna
• Dr. Neeraj Bijlani
• Dr. Vijay Kakatkar
• Dr. S S Mohanty
 Introduction to osteoporosis

• Osteoporosis is called a “silent” disease” since bone loss occurs without any specific symptoms,
until there is a fracture
 Prevalence

Global Prevalence
• The prevalence of osteoporosis in the world was 18.3%.
• Around 23.1% women and 11.7% men are affected by osteoporosis globally

Indian Prevalence
• In India, the prevalence of osteoporosis was 24.7%.
• The prevalence in women was reported to be 15%; whereas in men, it was reported to be 9.7%
 Impact of osteoporosis
• Quality of life
• In patients with osteoporosis and fractures, measuring health-related quality of life is important
marker to predict clinical evolution and functional changes.

• Quality of life (QoL) of these patients is significantly altered by physical, emotional, and
psychological incapacity, combined with the pain that results from hip, spine, or wrist fractures.

• Measuring the QoL will facilitate better osteoporosis treatments, thereby improving patient
health, reversing bone loss and reducing the risk of fractures
• Physical Function
• Osteoporosis and fracture can have a
profound impact on physical function
and everyday activity, and this impact
accumulates over time through a
cycle of impairment.

Figure 2: The cycle of impairment and fracture in osteoporosis 6

Pathophysiology of osteoporosis

• Deficiency (25(OH)D < 50

nmol/L) accelerates
bone turnover, bone
loss, and osteoporotic
fractures

Figure 3: Remodeling cycle and regulators of bone formation 9

 Effect of vitamin D on anti-inflammatory
mediators and its Immunomodulatory role

Figure 4: Vitamin D, immunological effects and impact on bone and endocrinological diseases. 7

ECM: extra cellular matrix; Th2: T helper 2 cells.

Management of osteoporosis
• The US Surgeon General has outlined a ‘pyramid
approach’ to treating bone diseases (Figure 5).

• Prevention of falls with maintenance of bone health

through adequate calcium, vitamin D, and physical
activity represent the base of the pyramid for all
individuals, including those with bone disease.

• The second tier of this pyramid relates to identifying and

treating secondary causes of osteoporosis.

• Lastly, the third tier revolves around pharmacotherapy Figure 5: The Osteoporosis Pyramid for Prevention and Treatment 10
Figure 6: Algorithm for the diagnosis and management of
Osteoporosis11
 Importance of nutrition in osteoporosis
• Once peak bone mass is achieved in late adolescence, bone health is optimized by maintaining as
much of this bone mass as possible throughout adulthood and prevention of bone loss with
aging.

• To obtain optimal efficacy of the prevention and treatment strategies, health care providers must
identify patients at risk for bone loss and diagnose bone thinning.

• Calcium and vitamin D have long been recognized as the critical nutrients necessary for bone
health and maintenance.

• In a patient with bone loss, the continuation of calcium and vitamin D is critical for optimal care.

• Unfortunately, around 90% of women are reported to have inadequate calcium levels and over
50% of women treated for bone loss have inadequate vitamin D levels.
 Prevalence of vitamin D deficiency in
patients with osteoporosis
Figure 7: Prevalence of vitamin D and secondary hy-
perparathyroidism in patients with fragility fractures11
80

• Vitamin D deficiency is prevalent in about 70

three fourths of hip fracture patients and

Percentage of patients
two thirds have secondary 60

hyperparathyroidism 50

40

30

20

10

0
Vitamin D deficiency Secondary hyperparathyroidism

Males Females
Vitamin D supplementation in osteoporosis
• The use of vitamin D supplement, especially vitamin D3 could reduce incidence of fall

• Daily supplement of 1000mg of calcium combined with 400 IU of vitamin D supplementation did
not significantly impact risk of hip fracture
 Vitamin D status and BMD
• Vitamin D status has a significant impact on bone mineral density (BMD), not only in vitamin D
deficient subjects, but also in vitamin D insufficient subjects.

Results of randomized clinical trials of vitamin D (and calcium) with BMD as (secondary) outcome criterion.

Ref Patients Vit D dose Calcium dose mg/d BMD increase

Chapuy 1992 56 f 800 IU/d 1200 Total hip + 7%, p <

0.001
Dawson-Hughes 1995 247 f 700 IU/d 500 Femoral neck + 1.5%, p
< 0.01
Chapuy 2002 114 f 800 IU/d 1200 Femoral neck + 2.5%, p
= 0.09
Harwood 2004 150 800 IU/d 1000 + 3%
Zhu 2008 120 f 1000 IU/d 1200 Total hip + 2%
 Vitamin D and bone turnover

• Increasing serum vitamin D levels

has a positive association on
markers of bone turnover.
Figure 8: Relationships between
serum 25(OH)D and bone
turnover markers
 Vitamin D for the prevention of fracture in
osteoporosis
• The preferred level for 25(OH)D is now
recommended by many experts to be > 30
ng/ml.
• Based on the literature, it appears that vitamin
D intoxication does not occur until blood levels
are above 150-200 ng/ml.
• Several reference laboratories recognizing the
recommendation by some experts that a
preferred level of > 30 ng/ml is most desirable.

Figure 9: Possible relationship between vitamin D

status and skeletal and extraskeletal health effects14
Benefits of vitamin D supplementation for
optimal skeletal health
• Vitamin D supplementation in suitable doses (60,000 IU/week) must be encouraged in those who
are deficient and the “at-risk” population and must be accompanied with appropriate age-related
calcium intake.
 Importance of High dose Vitamin D
supplementation
• A meta-analysis of 12 randomized controlled trials aimed
to determine the most effective vitamin D3 regimen for
vitamin D deficiency in postmenopausal women.18
Figure 10: Change in Change in the mean serum Vi-
tamin D levels after 60,000IU weekly dose vs 1000 IU
daily Vitamin D dose

• Daily maintenance doses ranging from 2000 to 45

4800 IU/day were the most effect 40

• It not only increased 25(OH)D to adequate levels, but 35

they consistently maintained it with continued therapy 30

• A prospective, randomized, observational study 25

compared the effect of oral high-dose vitamin D
20
regimens (60,000 IU weekly) and daily low-dose vitamin
D regimen of 1000 IU in a total of 90 patients with 15

vitamin D deficiency (serum levels < 30 ng/mL).19 10

• For high-dose vitamin D (60,000 IU weekly), the increase 5

in mean serum vitamin D levels from baseline was 0

significantly higher as compared to the low-dose group 60,000 IU weekly 1000 IU daily

(1000 IU daily) after a period of 10 weeks 60,000 IU weekly 1000 IU daily

Points to Ponder
• Weekly dose of 60,000 IU of vitamin D was more efficacious than daily dose of 1000 IU in
increasing the vitamin D level to normal range.
• High dose regimen may be a more convenient, effective, and economical mode of treatment for
patients with vitamin D deficiency.
• Need for rapid correction
• Optimal Serum levels for desirable effects
 Need for rapid correction of serum Vitamin D
levels
• An estimated amount of vitamin D in the range of 10,000 International units (IU) to 25,000 IU is
made in the skin by adequate daily sun exposure.
• Sunshine will not cause the body to over produce vitamin D and cause toxicity to occur.
• Assuming that all the vitamin D is acquired from the diet, and that all a person needs is 600 IU a
day, as recommended by the IOM, doesn’t appear to be adequate from a physiological
standpoint.
• Rapid correction of Vitamin D deficiency by giving 60,000 IU of Vitamin D3 each day for 10 days
maintains the level for 4-8 months and increases serum Vitamin D level by 8-10 ng/ml each day,
which can be achieved with short term-Rapid dose therapy.
• Supplementation with 60,000 IUs/day vitamin D for 10 consecutive days using the Pulse-D
therapy led to a significant improvement in vitamin D serum levels from ~16 to 81 ng/ml and
improvement in functional disability
 Treatment of symptomatic vitamin D deficiency in
adults

• The NOS Guideline on Vitamin

D and Bone Health
recommends an oral loading
regimen of vitamin D3
(cholecalciferol) for treatment
of deficiency up to a total of
approximately 300,000 units
vitamin D given either as
weekly or daily split doses
 Vitamin D toxicity
• Symptomatic vitamin D toxicity is uncommon, and elevated levels of 25(OH)D do not strongly
correlate with clinical symptoms or total serum/plasma calcium levels

• Cholecalciferol supplementation of 60,000 IU daily (420,000 IU in the first week) that is higher
than existing recommendations but helps in achieving 25(OH)D>50 ng/ml
 Monitoring
• All patients receiving pharmacological doses of vitamin D should have the plasma-calcium
concentration checked at intervals (initially weekly) and whenever nausea or vomiting are
present.23

• The National Osteoporosis Society (2018) recommends checking adjusted serum calcium 1 month
after completing the loading regimen or after starting vitamin D supplementation in case primary
hyperparathyroidism has been unmasked.

• Adjusted plasma calcium is recommended to be checked one month after completing the
loading regimen or after starting lower dose vitamin D supplementation in case primary
hyperparathyroidism has been unmasked. The presence of hypercalcemia ought to lead to
cessation of further vitamin D supplementation prior to investigation of the hypercalcemia
 Summary
• Osteoporosis is called a “silent” disease” since bone loss occurs without any specific symptoms,
until there is a fracture.
• Osteoporosis and fracture can have a profound impact on physical function and everyday activity,
and this impact accumulates over time through a cycle of impairment.
• Deficiency (25(OH)D < 50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic
fractures
• Vitamin D deficiency is prevalent in about three fourths of hip fracture patients and two thirds
have secondary hyperparathyroidism
• The use of vitamin D supplement, especially vitamin D3 could reduce incidence of fall
• The preferred level for 25(OH)D is now recommended by many experts to be > 30 ng/ml.
• Based on the literature, it appears that vitamin D intoxication does not occur until blood levels are
above 150-200 ng/ml.
• Several reference laboratories recognizing the recommendation by some experts that a preferred
level of > 30 ng/ml is most desirable?????
• Vitamin D supplementation in suitable doses (60,000 IU/week) must be encouraged in those who
are deficient and the “at-risk” population and must be accompanied with appropriate age-related
calcium intake.
• Weekly dose of 60,000 IU of vitamin D was more efficacious than daily dose of 1000 IU in
increasing the vitamin D level to normal range.
• High dose regimen may be a more convenient, effective, and economical mode of treatment for
patients with vitamin D deficiency.
• ‘Short term – High Dose therapy’ may help to achieve desired vitamin D levels rapidly
• Supplementation with 60,000 IUs/day vitamin D for 10 consecutive days using the Pulse-D
therapy led to a significant improvement in vitamin D serum levels from ~16 to 81 ng/ml and
improvement in functional disability
• Prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU is safely tolerated.
• Symptomatic vitamin D toxicity is uncommon, and elevated levels of 25(OH)D do not strongly
correlate with clinical symptoms or total serum/plasma calcium levels
• Cholecalciferol supplementation of 60,000 IU daily (420,000 IU in the first week) that is higher
than existing recommendations but helps in achieving 25(OH)D>50 ng/ml.
• Rapid correction of Vitamin D deficiency by giving 60,000 IU of Vitamin D3 each day for 10 days
maintains the level for 4-8 months and increases serum Vitamin D level by 8-10 ng/ml each day,
which can be achieved with short term-Rapid dose therapy.
 Clinical Practice points
• Target Vitamin D levels: Maintaining serum concentrations consistently >30 ng/mL is essential
to prevent the risk of fractures.
• Vitamin D supplementation in suitable doses (60,000 IU/week) must be encouraged in those who are
deficient and the “at-risk” population and must be accompanied with appropriate age-related calcium intake.
• Weekly dose of 60,000 IU of vitamin D was more efficacious than daily dose of 1000 IU in increasing the
vitamin D level to normal range.
• High dose regimen may be a more convenient, effective, and economical mode of treatment for patients
with vitamin D deficiency.
• ‘An estimated amount of vitamin D in the range of 10,000 International units (IU) to 25,000 IU is made in
the skin by adequate daily sun exposure.
• Assuming that all the vitamin D is acquired from the diet, and that all a person needs is 600 IU a day, as
recommended by the IOM, doesn’t appear to be sufficient from a physiological standpoint.
• ‘Short term – High Dose therapy’ may help to achieve desired vitamin D levels rapidly
• Supplementation with 60,000 IUs/day vitamin D for 10 consecutive days using the Pulse-D therapy led to a
significant improvement in vitamin D serum levels from ~16 to 81 ng/ml and improvement in functional
disability
• Prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU is safely tolerated.
 Advantages of Vitamin D entrapped in
Nano-Lipid CARRIER
Vitamin D molecules entrapped in Nano-
Lipid CARRIER
PH-Resistant Barrier and Enzyme-
Resistant Barrier
Outer Hydrophilic Layer
Size of nanoparticle is less than 150
Nanometer
Each Nano-lipid-carrier contains approximately 8000
molecules of Vitamin D3
Protects the Nano-Lipid-Carrier particles in harsh GI
environment, i.e. effect of varying pH conditions,
different enzymes and thus, facilitates Nano-entrapped
D3 to reach the enterocytic surface (for absorption)
Facilitates transportation of Nanoparticles through
unstirred aqueous layer of GIT
Space between 2 enterocytes being 150 nm, the
nanoparticles perfectly pass through the space between
2 enterocytes
Backed by Evidence
• Enhanced stability
• Predictable and consistent rise in 25(OH)D3 Levels
• Weekly dose achieves 50 ng/mL of 25(OH)D3 level adequate for addressing deficiency and
elevation in PTH
• Daily short-term (10 days) high-doses achieve 85 ng/mL adequate for addressing any skeletal,
extra-skeletal or immune pathologies
• Safety established in paediatric and adult populations irrespective of dosing schedule or
indication
• Evidence based formulation

Nanoparticle-based formulation of vitamin D3 is effective and safe in correction of vitamin D levels in patients with
documented deficiency or insufficiency of vitamin D.
 Objectives
1. Place of Oral Vitamin D3 in the treatment of Osteoporosis
2. Desired therapeutic levels of 25(OH)D3 in the above conditions?
3. Dosage and duration of Oral Vitamin D3 in the treatment.
4. Preferred option/s amongst various Vit D3 preparation
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