Download Men - Sex and Gender Specific Health

Treatment
• Promotes bone
formation and
decreases bone
resorption
Mechanism of
Action
Application
• First line treatment
for osteoporosis in
both men and postmenopausal
women1
Bisphosphonates
• Approved in both
sexes for the
prevention and
treatment of
osteoporosis
Aledronate2,
Risedronate3 and
Zoledronic Acid4
Ibandronate
(Boniva)
Only FDA approved for
treatment (not prevention)
of osteoporosis in postmenopausal women
Bisphosphonates
Not FDA approved
for males
• Paucity of studies1
• Similar
pharmocokinetics in
men and women2
• Similar efficacy in men
and women probable3
Drug
Route/
Frequency
Indicated
for which
gender
Alendronate
PO/QDay,
QWeek
Women
Men
Risedronate
PO/QDay,
QWeek,
QMonth
Women
Men
PO/QMonth
IV/Q3Mont
h
Women
IV/QYear
Women
Men
Ibandronate
Vertebral
Fracture
RR
Hip
Fracture
RR
NE
Nonvertebral
RR
NE
Zoledronic
Acid
Bisphosphonates
RR = Risk Reduction
NE = No effect demonstrated
Drug
Vertebral
Fracture
RR
Hip
Fracture
RR
Nonvertebral
RR
Route/
Frequency
Indicated
for which
gender
Raloxifene
NE
NE
PO QDay
Women
Calcitonin
NE
NE
Nasal QDay
SQ QDay
Women
Teriparatide
SQ QDay
Women
Men
Denosumab
SQ
Q6Months
Women
Men
RR = Risk Reduction
Other Agents
NE = No effect demonstrated
Estrogen & Bone Metabolism
HRT- Hormone Replacement Therapy
Estrogen’s protective role in bone metabolism has long been
appreciated1
Decline of estrogen in postmenopausal females provides a
ready example of estrogen’s protective role in bone
metabolism2
Estrogen HRT in postmenopausal women has been shown to:
• prevent bone loss (Maintain BMD)
• decrease bone remodeling and incidence of vertebral fracture3
Estrogen in Females
Testosterone’s
influence on bone
metabolsm is
minimal in both
sexes2
Estrogen has a
greater role in
preventing bone
resorption in both
males & females2
Testosterone &
estrogen decline
with aging1
Estrogen in Males
• Mechanism of Action: selective estrogen-receptor
modulator
– Benefits
• Increases BMD of hip and spine in women1
• Females: approved for treatment and prevention of
osteoporosis in women.
• Not approved in males2
– Narrow study contexts3,5
– Was not shown to significantly impact BMD in
males4
Raloxifene
• 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
• FDA approved for
– postmenopausal moderate/severe vasomotor symptoms
– prevention of postmenopausal osteoporosis.
• Increased hip and lumbar BMD
Tissue Selective Estrogen Complex
• Bazedoxifene/Conjugated Estrogen (Cont’d)
– Approved in Women for2
• prevention of osteoporosis
• osteopenia
• post menopausal vasomotor and sleep disturbances
– Men: None of the three major clinical trials included
men, despite that estrogen has been demonstrated to
play a significant role in bone formation3,4,5.
Tissue Selective Estrogen Complex
• Mechanism of Action
– Analogous to endogenous calcitonin
• Indications
– Approved for the treatment (not prevention) of
osteoporosis in women who are ≥5 years postmenopausal
– Not utilized in men
Calcitonin-Salmon
• Mechanism of Action: recombinant parathyroid hormone
(PTH); stimulates bone formation.
• Approved for
– Treatment & prevention of osteoporosis in men
and postmenopausal women1
– Especially those at high risk for vertebral fracture2
Teriparatide (Forteo)
Significantly increased lumbar
BMD from baseline levels3
Extent of lumbar BMD
increase similar in both males1
and postmenopausal females2
Teriparatide Efficacy
NOF
Recommended
Daily Intake:
Calcium
Men: 1000 mg
Women: 1200
mg
Vitamin D
Men &
Women: 800 –
1000 units
Calcium & Vitamin D
Total Fracture Incidence
• DIPART Group analysis
of 7 major Vitamin D and
Calcium trials in the US
and Europe.
• Analysis included 68,500+
patients
• Only 14% of subjects
were males
Calcium and Vitamin D
Hip Fracture Incidence
Calcium and 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 Demographics
• Men were understudied
• 2010 DIPART Group Meta-Analysis: only14%
of 68,500 subjects studied were men1
• 2007 Tang et al2. Meta-Analysis included only
8% men3
Calcium & Vitamin D
• Mechanism of Action: monoclonal antibody;
prevents osteoclast maturation.
“RANK-L”, RANK-Ligand
RANK-L Inhibitor (Denosumab)
• Approved to increase BMD in1,2
– Women:
• With non-metastatic breast cancer
• post-menopausal women with osteoporosis at high risk
for fracture.
– Men:2
• With non-metastatic prostate cancer who are receiving
Androgen Deprivation Therapy.
• With osteoporosis who are at high risk for fracture.
Denosumab (Prolia)
Efficacy in Males
Increased: BMD at all
skeletal sites (lumbar spine,
femoral neck, trochanter,
radius & total hip)
Decreased: serum bone
turnover markers, incidence of
vertebral fracture in those with
non-metastatic prostate cancer.
Denosumab
Efficacy in Females
Increased vertebral,
hip and non-vertebral
BMD1.
Decreased incidence of
vertebral, hip and nonvertebral fractures1,3
Denosumab
In Males,
• No data for fracture incidence in males without nonmetastatic prostate cancer1.
• Few phase III clinical trials have thoroughly investigated
the efficacy of Denosumab in males, though it has been
shown to be a beneficial treatment option.
In Females,
• Major phase III clinical trials studied Denosumab efficacy in
>2000 postmenopausal females2– no equivalent in males.
• Examples: FREEDOM, DEFEND, DECIDE & STAND
studies3
Denosumab Research Disparities