Place of HRT in bone health ?

1
Place of HRT in bone health ?

•  
• There still is a place
• Bruno Pornel
• Brussels Menopause Center

2
Albright's time, 1941

• Osteoporosis and Menopause
• estrogen deficiency, an important role in bone
  loss
• deficiency of formation, not of mineralization of
  bone matrix
• 40 of 42 patients with osteoporosis before age 65
  were women past menopause or young women
  postoophorectomy

3
Albright's time, 1941

• concluded that estrogen stimulates osteoblasts
  (!)
• by metabolic balance studies, estrogen causes a
  positive calcium balance
• long-term therapy arrested vertebral damage and
  height loss in postmenopausal osteoporosis and
  prevented them if started early.

4
Nordin's time, 1962

•  Postmenopausal osteoporosis is due to prolonged
  negative calcium balance occurring in subjects
  with a higher than normal calcium requirement or
  unable to adapt to an inadequate intake. 

Nordin B.E.C., American J. of Clinical Nutrition
10, 384-90, 1962 Young MM, Nordin BE. The effect
of natural and artificial menopause on serum and
urine calcium. Proc R Soc Med 196962242-245,
1969
5
Meema's time, 1963

• Numerous older studies
• bone loss either starts or increases at the
  time of the menopause.
• The effect of estrogen deficiency on the
  skeleton
• first shown in cortical bone of the metacarpal
  and radius

Meema HE. Cortical bone atrophy and osteoporosis
as a manifestation of aging. AJR
1963891287-1295.
6
Genant Ettinger's time, 1980

• Quantitative computerized tomography (QCT)
• independently measurement changes in trabecular
  bone
• very sensitive to the effect of estrogen
  deficiency.
• Bone loss from trabecular sites is 6 to 7 times
  greater than that from cortical sites

Cann CE, Genant HK, Ettinger B. Spinal mineral
loss in oophorectomized women determination by
QCT. JAMA 19802442056-2059
7
DEXAs time, 1986

• composite measure of cortical and trabecular
  bone. Changes smaller if measured by DXA compared
  with QCT
• spine small age-related decrease before
  menopause but a large change after menopause

Cann CE, Genant HK, Ettinger B. Spinal mineral
loss in oophorectomized women determination by
QCT. JAMA 244 2056-59, 1980
8
Biochemical Markers of Bone Turnover, Endogenous
Hormones and the Risk of Fractures in
Postmenopausal Women The OFELY Study

• cohort of healthy untreated younger
  postmenopausal women aged 50-89 years (mean, 64
  years)
• comparison baseline levels of bone markers and
  endogenous hormone
• follow-up 5 years
• 55 women subsequently had a fracture
• 380 women did not have a fracture

 Garnero P., Delmas P.. et al, JBMR 151526-36,
2000
9
Biochemical Markers of Bone Turnover, Endogenous
Hormones and the Risk of Fractures in
Postmenopausal Women The OFELY Study
 Garnero P., Delmas P.. et al, JBMR 151526-36,
2000
10
Biochemical Markers of Bone Turnover, Endogenous
Hormones and the Risk of Fractures in
Postmenopausal Women The OFELY Study
 Garnero P., Delmas P.. et al, JBMR 151526-36,
2000
11
Adjusted Associations between Serum Hormone
Concentrations and Vitamin Levels and the Risk of
Hip or Vertebral Fracture in Postmenopausal Women
Cummings S et al. N Engl J Med 339733-738, 1998
12
Serum Estradiol Concentration at Base Line and
Age-Adjusted Risk of Subsequent Hip or Vertebral
Fracture in Postmenopausal Women
Cummings S et al. N Engl J Med 339733-738, 1998
13
Effects of Estrogen Plus Progestin on Risk of
Fracture and Bone Mineral Density The WHI
Cauley, J. A. et al. JAMA 290 1729-38, 2008
14
Effects of Estrogen Plus Progestin on Risk of
Fracture and Bone Mineral Density The WHI
Cauley, J. A. et al. JAMA 290 1729-38, 2008
15
Effects of Estrogen Plus Progestin on Risk of
Fracture and Bone Mineral Density The WHI
Cauley, J. A. et al. JAMA 290 1729-38, 2008
16
Effects of Estrogen Plus Progestin on Risk of
Fracture and Bone Mineral Density The WHI
Cauley, J. A. et al. JAMA 290 1729-38, 2008
17
WHI Conclusion

•  the results of the WHI make estrogen the only
  drug demonstrably protective against osteoporotic
  fractures in a general population, as opposed to
  all other clinical trials with alternative
  osteoporosis therapies that have been tested and
  found efficacious only in patients with
  established osteoporosis .

Lindasy R., Early postmenopausal bone loss
symposium. 24th Annual Meeting of the ASBMR, San
Antonio, TX, 2002.
18
The Effects of Tibolone in Older PM
WomenLong-Term Intervention on Fractures with
Tibolone (LIFT)
Cummings S et al. N Engl J Med 359 697-708, 2008
19
Effects of Tibolone on New Fractures, According
to the Presence or Absence of a Vertebral
Fracture at Baseline
Cummings S et al. N Engl J Med 359 697-708, 2008
20
Two to three years of hormone replacement
treatment in healthy women have long-term
preventive effects on bone mass and osteoporotic
fractures the PERF study . 
Study A
Study B
HRT
HRT
0
0
PLB
PLB
-10
-10
-20
-20
0
5
10
15
0
5
10
15
YEAR
YEAR
Bagger YZ et al Bone 2004 34 728-735
21
Two to three years of hormone replacement
treatment in healthy women have long-term
preventive effects on bone mass and osteoporotic
fractures the PERF study . 

• 8 higher BMD
• 50 decreased risk of fracture

22
WIMALAWANSA S., JBMR,152240-2244, 2000
23
Nitroglycerin Therapy Is as Efficacious as
Standard Estrogen Replacement Therapy (Premarin)
in Prevention of Oophorectomy-Induced Bone Loss
A Human Pilot Clinical Study

• Previous animal studies have shown that NO donor
  therapy can prevent ovariectomy (OVX)-induced as
  well as corticosteroid-induced bone loss
• NG ointment applied to the skin once a day or
  CEE 0,625 mg

WIMALAWANSA S., JBMR,152240-2244, 2000
24
Nitroglycerin Therapy Is as Efficacious as
Standard Estrogen Replacement Therapy (Premarin)
in Prevention of Oophorectomy-Induced Bone Loss
A Human Pilot Clinical Study

• the first time that NG is as effective as
  estrogen in preventing bone loss in these
  surgically induced menopausal women
• dose of NG used in this study was three to four
  times less than that generally used
• NO increases osteoblastic activity and decreases
  osteoclastic activity

WIMALAWANSA S., JBMR,152240-2244, 2000
25
Estrogen Therapy and Coronary-Artery Calcification
Manson J et al. N Engl J Med 20073562591-2602
26
Place of HRT in bone health ?

• Osteopenia prevention yes
• Osteoporosis treatment yes

27
Place of HRT in bone health ?

• Thanks