Warning: include(../../js/fulltext.php): failed to open stream: No such file or directory in /home/suxhorbncfos/public_html/jgwh/JGWH.MS.ID.555859.php on line 2
Warning: include(): Failed opening '../../js/fulltext.php' for inclusion (include_path='.:/opt/alt/php56/usr/share/pear:/opt/alt/php56/usr/share/php') in /home/suxhorbncfos/public_html/jgwh/JGWH.MS.ID.555859.php on line 2 Treatment of Postmenopausal Osteoporosis
Osteoporosis occurs when bones loose their strength and density. Bones become fragile, weak and brittle and can cause fracture easily. Osteoporosis affects women after menopause and in their later years. The drop in estrogen after menopause is associated with increased loss of bone density for few years. Osteoporosis prevalent among older postmenopausal women increases the risk of fractures. Hip and spine fractures are associated with high morbidity and mortality among this population. Bone loss can be detected by measuring bone mineral density by densitometry. The primary goal of treatment of osteoporosis is to prevent a fracture which is accomplished by slowing /stopping bone loss, maintaining bone strength and minimizing that may contribute to fractures. This is done by change in lifestyle and diet and by giving pharmacological therapy.
According to WHO, Osteoporosis is now widely recognized as a progressive systemic disease characterized by low bone mineral density and micro architectural deterioration in the brain that predisposes the patients to increased bone fragility.
Osteoporosis is most common in women after menopause . Postmenopausal osteoporosis occurs when the rate of bone loss exceeds the rate of bone formation. Menopause typically occurs in women in the midlife during their 40s and 50sand signals the end of fertile phase of a woman’s life cycle. The transition from reproductive to non-reproductive phase is the result of a minor reduction in female hormone production by the ovaries. This transition occurs over a period of years and is a natural consequence of aging. The changes occurring during the transition can disrupt their daily activities. There are 1.5 million osteoporotic fractures every year, with an annual direct cost of treatment of $18 billion. Fractures occur because of qualitative and quantitative deterioration in the vascular and cortical skeleton. In other words, the body is breaking down bone as it normally does but it is not producing new bone. As a result, bones become fragile and weak. It is harder to heal after a fracture when one has osteoporosis, presenting a double threat for people with this condition [2-4]. The menopausal transition is associated with bone loss that exceeds 4% year and extends for 10 years or more .There is individual variation to the rate and extent of bone loss.
Women develop postmenopausal osteoporosis because estrogen rates declines after menopause. A lack of estrogen in postmenopausal women prevents the absorption and utilization of calcium and is the single most important factor in the development
of osteoporosis in older women. As women grow older, they can lose significantly, their bone mass which results in osteoporosis. It may be identified during routine medical check up or in the wake of fractures which do not heal properly. Osteoporosis can affect almost the entire skeleton. The disease often does not become clinically apparent until a fracture occurs .
The risk factors for osteoporosis are advancing age, low body weight, maternal history of osteoporosis, the direction of a fall and the most important, the presence of risk fractures- fracture wrist, spine, proximal femur or humerus after mild/moderate trauma and those with osteopenia or spinal deformities  (Table 1).
Estrogens are naturally occuring steroidal hormones produced by the ovary, adrenal gland and during pregnancy by the placenta. The major estrogen produced by these organs is estradiol which
they synthesise from cholesterol. Estradiol is metabolized in
the liver and form estriol and estrone, both of which are mildly
estrogenic and are excreted in the urine. Estrogens are most
implicated in the reproductive organs but also act upon other
organ systems such as CVS, Skeletal, Immune, GIT, neural sites.
Their major actions are genomic, mediated by nuclear organ
receptors but they may also have non- genomic actions .
Two estrogen receptor molecules have been identified. The
original estrogen receptor & the estrogen receptor beta. Their
structures are similar to those of other members of this family of
receptors. The key components are the C or DNA binding domain,
which binds with ligand binding affinity & sequence to DNA
sequences in the promoter region of target organ, which binds
estrogens & estrogen analogues.
The combined deficiency of calcitonin and estrogen has
been accorded pathogenetic significance. The circulating levels
of calcitonin tend to be lower in postmenopausal women.
This hormone directly inhibits osteoclast activity &hence
bone resorption. The local mediators include PGE2 formed by
the osteoblasts, can either increase bone resorption or bone
formation .Several osteoclast activating factors such as IL-1 &
transforming growth factors produced locally by the macrophages
and lymphocytes may contribute to regional bone resorption.
The resorption usually begins at the corticoendosteal surface,
resulting in enlargement of the medullary cavity and thinning
of cortex. Cancellous bone is also affected. The trabecular plates
may be converted to slender strands, sometimes it can result in
complete resorption or resection. Because the vertebrae have
thin cortex normally and depend on their structural integrity on
trabeculae, they are particularly often referred to as vertebral
crush fracture syndrome. The increased bone resorption is
reflected in an increased number of bizarre osteoclasts .
Postmenopausal bone loss progresses until the skeletal
fragility leads to pain in the back, spine such as lumbar lardosis
or kyphoscoliosis related to vertebral collapse. Overt fractures
most often are of distal radius, femoral neck and vertebral bodies.
Fractures in these three sites have a combined prevalence of 40 %
in women >65 years. These fractures result in 40, 00-50, 00 deaths
Bone quality can not be measured clinically, but bone mineral
density can be measured quickly and accurately. Bone mineral
density should be measured in women with strong risk factors
for osteoporosis. It should also be measured in those with
osteoporosis related fractures. Several techniques are available for
the measurement of bone mineral density. Among them the most
useful is dual energy X ray absorptiometry. With this technique
the density of the proximal femur is the most useful for predicting
fractures. The measurement of lumbar or spine density is most
useful for maintenance therapy. A T score of lower than -2.5
especially in the presence of risk factors, indicates the need for
treatment to prevent fractures. T score of less than -1 or a Z score
of less than -1 at the lumbar spine/proximal femur within five
years after menopause at any age indicates the need to prevent
bone loss. A z score of less than -2 indicates accelerated bone loss
and needs further studies to identify the risk factor [2,4,7].
It is important to screen the patients at risk and detect early
bone loss in accordance with WHO standards. Postmenopusal
women with established fractures should undergo an evaluation
for osteoporosis that includes a comprehensive medical and
family history and physical examination including vital signs and
assessment of routine lab testing should be done. It should include
C.B.C, serum calcium, phosphate, liver enzymes, total alkaline
phosphates, creatinine & electrolyte levels, thyroid functioning
testing and urinalysis [2,3].
Treatment focuses on non -pharmacological measures such as
balanced diet, adequate calcium and vitamin D intake, adequate
exercise, smoking cessation, avoidance of excess alcohol intake
and fall prevention. If pharmacological therapy is indicated, govt.
approved options are calcitonin, biphosphonates, glucosamine,
SERMS, Reclast, Teripatratide, transdermal estrogens and
hormone replacement therapy [10,11].
Calcium is most essential to bone health. The controlled
clinical trials examining the effect of calcium on bone density and
fractures in postmenopausal women, 15 trials (1806) patients
were included that randomized post menopausal women to
calcium supplementation and recorded bone mineral density of
the total body. The results showed that calcium supplementation
alone has small effect on bone density but there as reduction in
vertebral fractures. Calcium supplementation mostly increases
mineral density of non weight bearing, cortical bone. Calcium
salts are available in form of calcium carbonate, calcium citrate,
calcium maleate, calcium gluconate, calcium hydroxide, calcium
lactate, calcium sulfate, calcium pyrophosphate, calcium oxalate,
calcium pantothenate salts. Calcium carbonate is absorbed more
efficiently when taken with meals because it needs acid produced
by the body when food is in the intestine. In contrast ,calcium
citrate can be taken with or without food. Vitamin D increases
body’s efficiency at absorbing calcium. The best source of this
vitamin is from sunlight. Many dietary modifications can help
body absorb calcium more easily. A sodium and protein intake
impairs calcium absorption, while added potassium helps with
the absorption. Caffeine and alcohol can decrease the body’s
ability to absorb calcium. The national institute of health adds that
a diet high in fruit and vegetables shifts the acid base balance in
the body, decreasing calcium absorption. The recommended dose
of 1500mg of calcium and 400-800 IU of vitamin D daily can stop
bone loss for some postmenopausal women .
Calcitriol enhances absorption of calcium and phosphate
from intestine. The metaanalysis of these 5 studies suggested
a potentially important reduction in vertebral fractures with
the intake of vitamin D. Factors that can affect vitamin D intake
include decreased exposure to sunlight, decreased dietary intake
and absorption problems. The body’s use of vitamin D is enhanced
in the presence of Mg and boron. Alfacalcidiol is orally active used
in the dose of 1-2 microgms/day. It can increase bone mineral
density and reduce fracture incidence in the elderly population.
Cholecalciferol (vitamin D3) is used as granules for oral ingestion
and oily solution for I.M injection. Calcitriol 0.25 -1 microgms is
given orally daily or on alternate days .
The other vital nutrients synergistically promote the
maintenance of healthy bone tissue. For instances mega doses
of calcium in absence of other minerals such as magnesium may
contribute to abnormal soft tissue calcification. Oral supplements
with as much magnesium as calcium helps to prevent bone loss.
Mg increases the remineralisation of weight bearing trabecular
bone in post menopausal osteoporotic women. The daily dose of
magnesium is 200-300mg .
It is produced by C cells of the thyroid. It inhibits bone
resorption by direct action on osteoclasts. 30 studies were done
in post menopausal women on calcitonin treatment .Calcitonin is
shown to reduce the risk of vertebral fractures but the effect on
hip fracture appears to be less than that of biphosphonate therapy
.It is used in post menopausal osteoporosis as 100Usc or IM daily
along with calcium and vitamin D supplements. A nasal spray
formulation delivering 200 IU per actuation has become available
in some countries [15-17].
Etridronate, Alendronate, risedronate inhibit bone resorption.
Alendronate is administered empty stomach in the morning with
a full glass of water and patient is instructed not to lie down
or take food for at least 30min. It is available as 35 and 70mg
tablets. Recent data support the use of alendronate 10mg daily in
the treatment of steroid induced osteoporosis. The dose of 5mg
daily has been shown to prevent accelerated bone loss in newly
postmenopausal omen & may be useful for omen who are unable
to take estrogen sensitive cancers or clotting disorders.
Calcium, iron, antacids, mineral water, tea, coffee, fruit juice
interfere with Alendronate absorption. Side effects are git.
Irritation, gastric erosion, flatulence, body ache. Etidronate is
administered as orally or as intravenous. Adverse effects are
gastric irritation, bone pain. The dose is 5- 7.5mg/kg /day .
The randomized phase 11 trial is studying how well alendronic
acid works in preventing osteoporosis in patients undergoing
donor stem cell transplant. Reclast is specifically prescribed for
treatment of osteoporosis in postmenopausal women. It is a
bisphosphonic acid inhibitor of osteoclastic bone resorption. Once
administered, it rapidly moves to bone and preferentially localizes
at sites of high bone turnover. Reclast is supplied as 5mg in a
100ml ready to infuse solution for intravenous administration.
The recommended initial dose of the drug is a 5mg infusion once
a year given intravenously over no less than 15 minutes. Adverse
effects associated with the use of Reclast may include arthralgia,
pyrexia, hypertension, headache, myalgia, and pain in extremity,
influenza like illness & nausea [19,20].
It is also used for the treatment of osteoporosis in postmenopausal
women. It is usually reserved for women who cannot take
biphosphonates. In the dose of 2gms, it has dual action of increasing
bone formation as well as decreasing bone breakdown and it
has been shown to decrease the risk of hip and spine fractures.
Strontium seems to be associated with an increased risk of blood
clots in the veins .
The most advanced dietary supplements for the management
of bone and joint health include chondro- protective agents such
as high quality glucosamine that may decrease the inflammation.
A double blind clinical study states that glucosamine supplements
may increase the cartilage and fluid that surrounds the joints
or helps prevent breakdown of these substances .Glucosamine
is a nutrient supplement that serves the purpose of cartilage
building or lubrication of joints. Glucosamine helps the efficient
working of joints and tissues. Glucosamine sulfate also plays a
crucial role in the repair, maintenance and replacement of worn
out or damaged tissues. It is an important constituent of body
cartilage, soft tissue that protects the joint. Glucosamine sulfate
greatly helps in relieving the osteoporosis pain in knee joints .It is
suitable and effective treatment for mild levels of arthritis as well
as osteoporosis. The recommended dose of glucosamine sulfate
is 100mg in 1-2 capsules during the day at meal times with food.
Side effects of glucosamine are very few .
Selective estrogen receptor modulators like raloxifene and
tamoxifen have been marketed. Tamoxifen causes improvement in bone mass due to antiresorptive effect. Tamoxifen is effective
orally. The dose is 10-20mg BD. Raloxifene is an estrogen partial
agonist in bone and CVS system. Raloxifene prevents bone loss in
post menopausal women. Raloxifene is absorbed orally but has
low bioavailability due to extensive first pass metabolism. Its side
effects are deep vein thrombosis and pulmonary embolism. The
dose is 60 mg /day. It is preferably used in women who are 5 years
past their menopause .
In a clinical trial using transdermal delivery-0.1mg of 17-
beta -estradiol for days 1-21 and oral dose on day 11-21 of a
28 days cycle. Transdermal estradiol treatment is effective in
postmenopausal women with established osteoporosis in only
who had hysterectomy as the side effects of estrogen affect the
other women with uterus .
Teriparatide is used for the treatment of osteoporosis in post
menopausal women with an increased risk of fractures. It works
by decreasing the formation of bone and is given by daily injection
under the skin in the abdomen or thigh. The recommended dose of
teriparatide is 20mg injected OD. It is good to take teriparatide at
the same time each day. It decreases incidence of spinal fractures
Hormone replacement therapy remains a valuable option
for the prevention of osteoporosis in elderly post -menopausal
women. The choice of treatment depends on age, the presence/
absence of prevalent fractures, esp. at the spine and the degree
of bone mass density measured at spine and hip. The study of
osteoporotic fractures provided epidemiological data that bone
loss continues in older women & that estrogen may decrease this
loss. Hormone replacement therapy is available as conjugated
equine estrogens in the dose of 0.625mg /day regularly or in
cyclic fashion. plus medroxyprogesterone acetate 2.5mg/day
or estrogen therapy. A 2002 study from Wake Forest University
School of Medicine indicates that stopping HRT does not appear
to accelerate loss of bone in post menopausal women. The study
also showed that while bone mass increased substantially in the
first 36 months after starting HRT. There was little gain in bone
mass after that. Among women who remain on HRT for upto 5
more years, it appears that bone mass remains stable at the same
level as 3 year treatment. But potential risks associated with
HRT included are an increased risk of venous thrombosis, an
exacerbation of preexisting liver disease for women with intact
uterus taking estrogen alone and an increased risk of endometrial
carcinoma. Serious side effects of hormone replacement therapy
include enlarged and tender breasts, nausea, skin discolouration,
water retention, weight gain, headache and digestive problems
Exercise greatly reduces the risk of heart disease, high B.P and
diabetes. It has positive effects on mental well being also. The sort
of exercise that is beneficial in preventing osteoporosis is weight
bearing such as walking or aerobics. Stopping smoking should be
a priority to enjoy a longer life. Alcohol consumption should also
be kept in safe limits.
Osteoporosis represents an increasingly serious problem
around the world. The economic burden of disease imposes is
already considerable and will further grow as the population
ages. It incorporates multiple modalities of therapy. In addition
to early detection, patient education, exercise and nutritional
supplementation, multiple therapeutic agents should be
implemented early in an attempt to prevent initial and subsequent
Results of large placebo controlled trials have shown that
alendronate, raloxifene, risedronate, 1-34 fragment of parathyroid
hormone and nasal calcitonin greatly reduced the risk of vertebral
fractures. Calcium along with vitamin D is most important for
increasing bone strength and vitamin supplementation is not
sufficient to treat individuals with osteoporosis but is useful sp.
in elderly women in care homes. Hormone replacement therapy
remains a valuable option for the prevention of osteoporosis in
post menopausal women. Choice of treatment depends on age,
the presence or absence of prevalent fractures, esp. at the spine
and the degree of bone mineral density measured at spine and
hip. Non-pharmacological intervention include adequate calcium
intake and diet, selected exercise programmes, reduction of other
risk factors for osteoporotic fractures. The overall benefit versus
risk assessment is a central focus in each of the clinical trial