Bisphosphonates are first-line treatment for osteoporosis in men and post-menopausal women by promoting bone formation and decreasing resorption. While alendronate, risedronate, and zoledronic acid are approved for both sexes, ibandronate is only FDA-approved for treating osteoporosis in post-menopausal women. Studies of ibandronate's efficacy and safety in men are limited. Calcium and vitamin D supplementation reduces hip, vertebral, and total fracture risk in both men and women, but men have been inadequately studied in trials. Research on osteoporosis therapies has primarily focused on post-menopausal women,

1. Bisphosphonates
• Mechanism of Action: promotes bone formation and
decreases bone resorption.
• Application: considered first line treatment for osteoporosis in
both men and post-menopausal women.1
– Aledronate2, Risedronate3 and Zoledronic Acid4: are
approved in both sexes for the prevention and treatment of
osteoporosis.

2. Bisphosphonates
• Ibandronate (Boniva): only FDA approved for use
in the treatment (not prevention) of osteoporosis in
post-menopausal women
– Not FDA approved for males
• Paucity of studies1
• Similar pharmocokinetics in men and women2
• Similar efficacy in men and women probable3
(statement made in the Orwoll study)
Dr. Jenkins: the STRONG study is the only one of its kind that I could find for
Ibandronate testing in males– in the speaker notes I wronte that it’s “one of the only
studies”– I hestistate to write “the only study” of its kind though—do you know of
similar studies?

3. Ibandronate Efficacy in Males
Percent change in L1-L3 BMD Percent change in TH BMD
TH- Total Hip. BMD- Bone Mineral Density.

4. Ibandronate Efficacy in Males
Percent change in sCTX Percent change in BSAP
C-terminal telopeptide of type 1 collagen (sCTX); Bone-specific alkaline phosphatase (BSAP)

5. Bisphosphonates
Drug Vertebral
Fracture RR
Hip Fracture
RR
Non-
vertebral RR
Route/
Frequency
Indicated
for which
gender
Alendronate PO/QDay,
QWeek
Women
Men
Risedronate PO/QDay,
QWeek,
QMonth
Women
Men
Ibandronate NE NE PO/QMonth
IV/Q3Month
Women
Zoledronic
Acid
IV/QYear Women
Men
RR = Risk Reduction NE = No effect demonstrated
Side effects: Heartburn, nausea, bone pain, infusion reaction (zoledronic acid)

6. Other agents
Drug Vertebral
Fracture
RR
Hip
Fracture
RR
Non-
vertebral
RR
Route/
Frequency
Indicated
for which
gender
Raloxifene NE NE PO QDay Women
Calcitonin NE NE Nasal QDay
SQ QDay
Women
Teriparatide NE SQ QDay Women
Men
Denosumab SQ
Q6Months
Women
Men
RR = Risk Reduction NE = No effect demonstrated
Side Effects
• Raloxifene – hot flashes, edema, arthralgia, increased risk of thromoembolism
• Calcitonin – flushing, rhinitis, nausea, back pain, local site reaction (SQ)
• Teriparatide – hypercalcemia, orthostatic hypotension, dizziness, nausea,
injection site reaction
• Denosumab – dermatitis, arthralgia, edema, bone pain

7. Raloxifene
• Mechanism of Action: selective estrogen-receptor modulator,
– Benefits: shown to increase BMD of hip and spine in women1
• Application: approved for treatment and prevention of osteoporosis in
women; not approved for use in males2.
• Study disparities in males
• Narrow study contexts3,5
• Raloxifene is understudied in males was not shown to significantly
impact BMD in males4
Duschek study cited in the notes section is the only one I could find conducted in healthy
males—the sample size was only 30 men! Is there another study out there that I’m missing?

8. Salmon Calcitonin
• Mechanism: inhibits absorption of calcium from intestine and
renal tubules; inhibits osteoclast activity.
• Indications: approved for the treatment (not prevention) of
osteoporosis in women who are ≥5 years post-menopausal
• Approval- FDA doesn’t mention if it’s approved in men as
well– they only state post menopausal women– is Salmon
calcitonin used in men clinically?

9. Calcitonin Efficacy
Percent change in lumbar spine
BMD
Percent change in femoral neck
BMD
sCT- salmon Caclitonin

10. Teriparatide (Forteo)
• Mechanism of Action: recombinant parathyroid hormone
(PTH); stimulates bone formation.
• Approval: approved for treatment and prevention of
osteoporosis in both men and postmenopausal women1 at high
risk for vertebral fracture. 2

11. Teriparatide Efficacy
Efficacy in Males1
Efficacy in Postmenopausal
Females 2

12. Calcium
• NOF Recommended Daily Intake: 1000 mg (men) and
1200 mg (women)
• Dietary Sources of Calcium
– Milk and other dairy products
– Fortified cereals
– Sardines
– Tofu
– Salmon
– Dark leafy green vegetables
National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of
Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.

13. Vitamin D
• NOF Recommended Daily Intake: 800 – 1000 units
• Dietary Sources of Vitamin D
– Oily fishes
• Salmon
• Tuna
• Flounder
• Sole
– Egg yolks
– Liver
– Mushrooms
– Fortified cereals & dairy products

14. Calcium and Vitamin D
Total Fracture Incidence

15. Calcium and Vitamin D
Hip Fracture Incidence

16. Calcium & Vitamin D
• Efficacy: combination Calcium (1200 mg) and
Vitamin D (800 mg) reduces the risk of hip,
vertebral and total fractures in both men and
women1.
• Study flaws: men have not been adequately studied.
– 2010 DIPART Group Meta-Analysis: only14% of 68,500
subjects studied were men1.
– 2007 Tang et al2. Meta-Analysis included only 8% men3.

17. Tissue Selective Estrogen Complex
• Bazedoxifine/Conjugated Estrogen (Duavee)
– Mechanism of Action: SERM that selectively
stimulates lipid metabolism and bone, however, has
no effect on the uterus and breast.
– Benefits
• Increased hip and lumbar BMD
• Improves post menopausal vasomotor symptoms and
sleep disturbances.

18. Tissue Selective Estrogen Complex
• Bazedoxifene/Conjugated Estrogen (Cont’d)
– Application: approved2 for prevention of osteoporosis,
osteopenia & post menopausal vasomotor and sleep
disturbances in post-menopausal women.
– Men: None of the three major clinical trials included men,
despite that estrogen has been demonstrated to play a
significant role in bone formation3.

19. RANK-Ligand Inhibitor
• Denosumab
– Mechanism of Action: monoclonal antibody; prevents
osteoclast maturation.
– Benefits: significant increase in lumbar BMD and reduced
risk of vertebral fracture in both men and women

20. RANK-Ligand Inhibitor
• Indications
– Women: approved for treatment in women with non-
metastatic breast cancer and post-menopausal women with
osteoporosis at high risk for fracture.
– Men: approved for vertebral fracture prevention in men
with non-metastatic prostate cancer who are receiving
Androgen Deprivation Therapy.

21. 139,647
subjects
♂
16,757
♀
122,889
J Clin Endocrinol Metab. 2012 Jun;97(6):1871-80
Osteoporosis Research

22. Post-Operative Mortality
• Men have higher early post-operative mortality and are
less likely to return to independent living or mobility.
• Women are almost twice as likely to survive at 30 days
compared to men (OR 1.93; 95% CI 1.73 to 2.14)
• Women are almost twice as likely to survive at 120 days
compared to men (OR 1.98; 95% CI 1.84 to 2.14)
• Women are more likely to return to their home by 120 days
post-fracture (OR 1.19, 95% CI 1.06-1.32)
• Women are more likely to return to walking unaided at 120
days compared to men (OR 1.25; 95% CI 1.11 to 1.41)

23. Osteoporosis Research
• Research bias
– Majority of research focused on post-menopausal women
– Trials in men
• Outcome of interest rarely hip fracture
• FDA requires vertebral data in men}} CLARIFY THIS–
FIND THE DATA IN ONE OF THE ARTICLES MJ
SENT YOU.
• For agents with hip fracture data in women, if vertebral
BMD gains are similar in men to those seen in women,
data is extrapolated to hip fracture reduction for men
Put that 1 slide that had the Numbers of men v women that MJ sent you.

24. Osteoporosis Research
• Cost effectiveness and Screening
– Women: Cost effective screening methods in women have
been studied adequately and has lent to the use of FRAX
and WHO BMD T-Scores in identifying treatment
candidates.
– Men: Cost-effectiveness has not be adequately studied in
men.
• FRAX underestimates fracture in men.
• NOF guidelines for treatment should be used
conservatively in men.

25. Percentage of non-vertebral, hip, upper humerus and wrist fractures that occurred in men and women with osteoporosis, osteopenia
or normal BMD using gender specific T -scores.
Still need to ask for permission.