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OSTEOPOROSIS: KEY ISSUES IN MANAGEMENT
Ambrish Mithal* and Nidhi Malhotra#
From the Senior Consultant in Endocrinology*, DNB student in Endocrinology#, Indraprastha Apollo Hospitals,
Sarita Vihar, New Delhi 110 076, India.
Correspondence to: Dr. Ambrish Mithal, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India.
Osteoporosis is a disease characterized by low bone mass with micro architectural deterioration of bone tissueleading to enhance bone fragility. This increases the susceptibility to fracture. Osteoporosis is a major publichealth problem. Hip fractures are the most devastating consequence of osteoporosis. Osteoporosis isessentially an asymptomatic disease. Medical evaluation includes complete history and examination toidentity risk factors, secondary causes of osteoporosis, and secondary complications of fractures. Low bonemass can only be diagnosed by measuring bone mineral density (BMD) by various techniques of which thegold standard is DEXA. Current management strategies include nonpharmacological measures like regularexercise, Calcium and vitamin D rich healthy diet, abstinence from smoking and prevention of falls.
Pharmacological measures include Anticatabolic drugs like Bisphosphonates (Alendronate, Risedronate,Zoledronate). SERMs. Estrogen, Calcitonin, and anabolic drugs like Teriparatide, and Strontium. Correction ofmetabolic abnormalities by judicious use of calcium and vitamin D is desirable before initiating specific drugtreatment. Ralixifene, Estrogen and Strontium are used in mild osteoporosis, Bisphosphonates arerecommended in moderate to severe osteoporosis and Teriparatide use is indicated in severe osteoporosiswith fractures. Calcitonin is used as adjuvant especially for its adjuvant effect.
Osteoporosis, Hip fracture, DEXA, Bisphosphonates, Teriparatide, Calcium, Vitamin D.
OSTEOPOROSIS is a disease characterized by low bone mass
results in fractures which may occur on trivial activities
with micro architectural deterioration of bone tissue leading
like fall from standing height, lifting heavy objects, sudden
to enhance bone fragility. This increases the susceptibility
jerks, coughing, sneezing etc. Vertebral fractures may
present as severe back pain, loss of height, and spinaldeformities like kyphosis, stooped posture etc. Hip
fractures are the most serious consequence of
(1) Osteoporosis is a major public health problem. There
osteoporosis; sometimes the patient falls as a result of the
is rapid increase in aging population in India.
spontaneous hip fracture (as opposed to a fall causing the
(2) Normally, one out of two women suffer from
osteoporosis beyond age 50 and one out of 4 have
Medical evaluation includes complete history and
examination to identify risk factors, secondary causes of
(3) Hip fractures are the most devastating consequence of
osteoporosis, and secondary complications of fractures.
osteoporosis (20% mortality, another 25% require life
In addition, the patient’s risk of falling should be assessed-
time assistance). Recent data suggests that multiple
poor vision, overall frail health, unsteady gait, instability,
vertebral fractures have major impact on the quality of
neurological disorders and the use of sedatives are
life, although their overall impact is less than that of
Certain laboratory tests are needed in all patients:
(4) Although solid data are not yet available, in India the
complete blood count, serum calcium, phosphorus,
risk may be even higher due to associated nutritional
alkaline phosphatase, liver and renal function tests.
Additional laboratory evaluation includes serum PTH,
(5) Average osteoporotic fractures occur 10-20 years
TSH, 25 hydroxy vitamin D and serum protein
earlier in India. Earlier diagnosis and treatment can
Low bone mass can only be diagnosed by measuring
Osteoporosis is essentially an asymptomatic disease. It
bone mineral density (BMD) by various techniques, of
Vol. 3, No. 2, June 2006
markers can distinguish such fast losers from average
Table 1. Evaluation of osteoporosis.
bone specific alkaline phosphatase and
osteocalcin (bone formation markers) and urinary N-telopeptide, C-telopeptide and PINP (bone resorption
markers). These bone turnover markers are suppressed to
To rule out secondary causes of bone loss
50% within 3 months of starting antiresorptive therapy.
Hematological disease and malignancy
This allows earlier identification of non-responders.
Complete blood count,ESR or CRP,Serum protein
However, they can’t be used to diagnose osteoporosis or
CURRENT MANAGEMENT STRATEGIES
Metabolic bone disease
Serum calcium, phosphorus, alkaline phosphatase,
Regular physical exercise, especially weight
bearing and muscle strengthening exercise, delays the
physiologic decrease of BMD that occurs with ageing
24 hr urine free cortisol, serum estradiol, testosterone,
(Ernst, 1998). One beneficial effect of exercise in the
elderly is likely to be the reduction in the risk of fallingthat result from improved muscle strength and co-
Chronic renal disease and Malabsorption
Serum creatinine, Endomyseal antibodies to excludeceliac sprue
The nutrients known with certainty to be
important are calcium, vitamin D, and protein.
Phosphorus, certain trace minerals (manganese,
which the gold standard is DEXA (Dual energy X-ray
copper, and zinc), and vitamins C and K, while
Absorptiometry). BMD assessment confirms diagnosis,
involved in bone health generally, are less certainly
detects disease in asymptomatic state, predicts chances of
involved in osteoporosis. A well balanced diet
future fractures, and is also useful for monitoring response
providing 1.2 g of calcium and 800 IU of vitamin D
should be recommended for women of all ages.
WHO criterion for diagnosis of osteoporosis is based
) Fall prevention:
Most fractures other than vertebral
on ‘T’ score (Table
2). T score depicts the bone density of
fractures are associated with falls. With increasing age,
a person when matched to young adult normal bone (which
falls become more frequent and the risk of injury from
corresponds to peak density of a 30-year-old person).
any single fall also increases. Therefore prevention of
‘Z’ score denotes the bone density of a person when
falls is likely to reduce the incidence of fractures
in elderly women. Hip protectors should be re-
There are factors other than BMD that help in assessing
the risk of Osteoporotic factures (Table
3). Five to ten per
) Smoking cessation:
Smoking increases bone loss. It
cent of all menopausal women is fast losers of BMD and
also reduces the beneficial effects of postmenopausal
hence has a higher risk of fracture. Bone biochemical
Table 2: World Health Organisation criterion for the diagnosis of osteoporosis 1994.
A value for BMD that is not more than 1 SD
A value for BMD that lies between 1 and 2.5 SD
the young adult mean value in the presence
Vol. 3, No. 2, June 2006
is insufficient to meet either the demands of growth or the
TABLE 3: Secondary causes of osteoporosis
drain of cutaneous and excretory losses, resorption will bestimulated by PTH (parathyroid hormone) and bone mass
Calcium and vitamin D supplementation
reduces bone loss and fractures at all ages especially in
elderly. They are, however, usually not used as the sole
treatment of osteoporosis, but as essential adjuncts to
treatment. The fact that vitamin D deficiency osteomalacia
is very common in urban Indians , it is necessary to
ensure adequate intake of Calcium and vitamin D before
Cancer (especially hematological conditions,
embarking on any pharmacological therapy for osteo-
porosis. Many experts now feel that at least 800 IU of
Congenital disorders (osteogenesis imperfecta,
vitamin D and 1.2 g of calcium are required daily by every
10. Neurologic disorders (including immobilization and
) Nitrogen containing compounds Alendronate,
Risedronate, Pamidronate, Zoledronate.
) Non-nitrogen containing compounds: Etidronate,
According to the latest nomenclature, the anti
Osteoporotic drugs have been classified into anti-catabolic
Mechanism of action
and anabolic, depending on their effects on boneremodeling and with respect to the mechanisms of fracture
They act by binding avidly to mineralized bone
surfaces and reduce bone turnover, largely by decreasingactivation frequency and the recruitment of osteoclast
: These drugs increase the bone
precursors, but they also reduce the amount of bone
strength by decreasing bone remodeling (less BMUs
removed during the resorption phase of the BMU cycle by
are formed) that leads to preservation of skeletal
either decreasing osteoclast work capacity or by increasing
microarchitecture. They reduce the bone turnover largely
apoptosis. They should be taken first thing in the morning
by decreasing Activation frequency and recruitment of
with water, and 30 minutes before the first food, drink or
osteoclast precursors. The fracture reduction associated
oral medication to be taken that day. Patient should remain
with anticatabolic drugs is largely caused by inhibition of
upright for at least 30 mins. Bisphosphonates currently in
high bone turnover, independent of its effect on preventing
These drugs increase the bone strengthby increasing bone mass substantially as a result of an
Alendronate (10 mg/day) after 3 years of
overall increase in bone remodeling (more BMUs are
treatment produces a vertebral fracture risk reduction of
formed) combined with a positive BMU balance (the
47%, non- vertebral (osteoporotic) fracture risk reduction
magnitude of the formation phase is more than that of the
of 36% and hip fracture risk reduction of 51% (Fracture
resorption phase). This results from the combination of
intervention trial) . It also reduces bone turnover
increased osteoblast function and an inhibition of
markers by 50-70%. Once weekly dosing improves patient
apoptosis that extends osteoblast life span.
compliance and also pharmacokinetics of the drug.
Although 10 years of alendronate treatment appears to
Calcium and vitamin D
be safe, the optimal duration of treatment has not beenestablished .
Supplementary calcium and vitamin D are generally
given with other anti catabolic agents as enhancers whose
small, but significant, effects depend mainly on whether
The recommended dose of alendronate for prevention
of postmenopausal osteoporosis is 5 mg/day or 35 mg/
Mechanism of action:
Whenever absorbed calcium intake
week and for treatment is 10 mg/day or 70 mg/week. For
Vol. 3, No. 2, June 2006
treatment of corticosteroid-induced osteoporosis, the
to be much more acceptable to patients and could reduce
indicated dose is 5 mg/day for men and estrogen replete
women and 10mg/day for postmenopausal women.
Single annual dose of 4 mg is given as an intravenous
While first and second generation bisphosphonates are
known to have gastrointestinal side effects, Risedronate is
In trials of treatment with zoledronic acid for
bone metastasis, 9-15% of the patients developed renal
It increases BMD by 3-6% and reduces bone turnover
by 40-60%. Risedronate (5 mg/day) taken over a period of3 years produces a vertebral fracture risk reduction of 41%
and non-vertebral fractures risk reduction of 40% (VERT
It recently got FDA approval for its use as a once
The approved dose is 5 mg/d or 35 mg/wk. It seems to
Significant reduction in new vertebral fractures in both
have better GI tolerability as compared to Alendronate.
treatment arms (62% and 50% respectively, versus
According to a recent Gastroenterology study, both
placebo), was observed after 3yrs in women with
Alendronate and Risedronate have mucosal irritative and
established postmenopausal osteoporosis . Both
healing impairing effects in the stomach, yet the effect of
treatment groups also produced a statistically significant
Risedronate was much less pronounced compared to
relative risk reduction in clinical vertebral fractures
(49% and 48% for daily and intermittent ibandronate,
respectively). The incidence of non-vertebral fractures wasfound to be similar in both ibandronate and placebo
It is approved by the FDA for treatment of hyper-
calcemia of malignancy and Paget’s disease of bone.
Recently, oral intermittent ibandronate administered
once a month was shown to be therapeutically equivalent
It has been shown to increase BMD or prevent bone
to daily oral regimen thus demonstrating the feasibility
loss in patients with post menopausal osteoporosis and
of once monthly dosing in the management of post-
corticosteroid induced osteoporosis.
It is given as an initial dose of 90 mg I/V with
It is approved as a once daily oral tablet (2.5 mg/day)
subsequent doses of 30 mg every 3rd month.
and also as a once monthly oral tablet in postmenopausalosteoporosis with recommended dosage of 150 mg on the
same date each month. This drug requires a more
It is the most potent bisphosphonate currently available.
prolonged 1 hr fast for adequate absorption as compared
Intravenous administration of zolendronate is also
to other bisphosphonates. Ibandronate is also the first
considered a superior alternative to oral bisphosphonates
bisphosphonate with the potential for administration by IV
in osteoporosis which are known to carry some limitations
injection over 10 to 20 secs without adversely affecting
related to long term compliance, gastrointestinal
intolerance and poor and variable absorption from
Estrogen deficiency is associated with an increase in
the secretion of cytokines IL-1, IL-6, TNF, M-CSF, RANK
At 12 months zoledronic acid regimens were associated
Ligand. Increased cytokine activity results in the
with deceases of 49 to 52% in serum CTx and deceases of
recruitment and activation of more osteoclasts which leads
54 to 65% in serum NTx, increase in lumbar spine bone
to increased bone resorption. Estrogen treatment reverses
density by 4.3 to 5.1%, femoral neck bone density by
3.1 to 3.5%, with no significant difference among
various zoledronic groups. Therefore, administra-tion ofzolendronate at intervals of 6 to 12 months or more is likely
In the WHI trial HRT reduced the risk of hip and
Vol. 3, No. 2, June 2006
vertebral fractures by 34% and of all other osteoporotic
fractures by 24%. This reduction was nominally significant
Raloxifene is taken as a once daily tablet (60 mg/day).
for all fractures. After 3 years of treatment, total hip BMD
Side effects include thromboembolic disease (Relative risk
was increased by 3.7% in the HRT group compared with
similar or lower than that of HRT), flu syndrome, leg
However, the overall results show that health risks
It is a polypeptide hormone that exerts its hypocalcemic
outweigh these benefits of HRT. Women’s Health Initiative
effects directly by inhibiting osteoclast resorption.
study (WHI), and the Million Women study, haveconfirmed that the use of HRT does not reduce the risk of
CHD and increases the risk of breast cancer, stroke and
Calcitonin, a weak anti catabolic drug, has been shown
venous thromboembolic events. As a result of these
to increase the lumbar spine BMD in late post menopausal
findings, other antiresorptive agents are now the drugs of
women by an average of 1-2%. According to the PROOF
choice for the prevention and treatment of osteoporosis in
study there was a 33% reduction in the risk of new
postmenopausal women. Use of HRT is presently limited
vertebral fractures in 200 IU calcitonin treated group.
to postmenopausal women with severe hot flushes and
Calcitonin has no effect on non vertebral fractures .
vaginal and skin changes. HRT should be used for theshortest time possible, at as low a dose as possible in order
Treatment of calcitonin should be considered for older
to stop the menopausal symptoms (hot flushes) and only
women with osteoporosis on multiple medications on those
who fail to respond / tolerate other treatments and in acutevertebral fractures because of its analgesic effect.
Estrogens are used orally at a dose of 0.3 mg/d for
esterified estrogens, 0.625 mg/d for conjugated equine
It is currently available as a parenteral and nasal spray
estrogens and 5 mcg/d for ethinyl estradiol. For
formulation. Administration of salmon calcitonin should
transdermal estrogen the recommended dose is 50mcg
be as 200 IU daily in alternating nostrils or 100 IU
estradiol per day. In women with an intact uterus, progestin
parenterally. Nasal calcitonin can produce rhinitis and
is added to reduce the risk of uterine cancer.
parenteral calcitonin may cause facial flushing, nausea andvomiting.
SERMS (Selective estrogen receptor modulators)
This group includes drugs like Tamoxifen and
Raloxifene that have tissue- specific effects in classical
TERIPARATIDE rhPTH (1-34)
target tissue for estrogen action. Raloxifene like Tamoxifen
It is the 1-34 amino acid fragment of the native 84
has antiresorptive effects on bone, but, unlike Tamoxifen,
amino acid parathyroid hormone molecule. PTH is an
it does not cause endometrial stimulation.
PTH exerts its action on bone through PTH1 receptor.
It can produce both bone resorption and bone formation.
According to the MORE (Multiple Outcomes of
Continuous exposure to high dose PTH increases
Raloxifene Evaluation) trial, Raloxifene (60 mg/day) after
osteoclast differentiation and action leading to bone
3 years of treatment, showed positive effects on bone
resorption. In contrast daily injections of low dose PTH
mineral density at lumbar spine and femoral neck (2-3%
(intermittent exposure) produces increase in osteoblast
increase). These increased over time and were independent
number and function leading to bone formation.
of dose. The relative risk reduction of new vertebralfractures produced was 30% to 50%. Raloxifene does not,
however, have a significant effect on nonvertebral fractures.
Randomized controlled trials have demonstrated the
efficacy of human parathyroid hormone, (hPTH (1-34), in
Apart from the skeletal effects Raloxifene induces a
improving bone mass and reducing the risk of fractures in
dose dependent decrease of serum total and LDL
postmenopausal osteoporosis. In an international fracture
cholesterol and may reduce the risk of cardiovascular
prevention trial, compared with placebo, teriparatide
events especially in women with increased cardiovascular
significantly reduced the risk of vertebral fractures by
65-69% and nonvertebral fragility fractures by 53-54%
Vol. 3, No. 2, June 2006
. In addition to postmenopausal osteoporosis,
fractures and 36% for hip fractures in group at high
Teriparatide is also a potentially useful therapeutic agent
for osteoporosis in men. Orwall, et al
. reported increase in
spinal bone mineral density by 5.9% (20 mcg) and 9.0%(40 mcg), femoral neck bone density by 1.5% (20 mcg)
Daily oral dose of 2 mg/day. Strontium is well tolerated
and 2.9% (40 mcg) and whole body bone mineral content
in upper gastrointestinal region. However, it has been
by 0.6% (20 mcg) and 0.9% (40 mcg) above baseline after
known to be one of the causal agents for osteomalacia in
11 months of teriparatide therapy (once daily).
patients with end stage renal failure on dialysis .
Patients are usually considered for Teriparatide
Treatment guidelines can be divided into 3 groups
[rhPTH(1-34)] treatment either because they remain
) Asymptomatic patients who need screening for
severely osteoporotic or because they have failed
antiresorptive therapy. Prior use of antiresorptives hasshown to produce variable effects on PTH action. Ettinger
) Patients with definite Osteoporosis.
et al. reported that prior treatment with Raloxifene allows
) Patients with fracture due to osteoporosis
for the Teriparatide induced BMD increases. In contrast,
(i) Asymptomatic patients who need screening
prior treatment with Alendronate prevents increases in
BMD, particularly in first 6 months . According to astudy by Cosman et al. PTH when added to HRT, in women
All postmenopausal women ( 65 yrs should routinely
with osteoporosis, produced significant increase in bone
undergo a bone density test to assess baseline status.
mass and density, this elevation persisted for 1 year
after discontinuation of PTH while women continued
< 65 yrs should be obtained if there is presence of risk
BMD is not recommended routinely in premenopausalwomen, but start prevention with calcium/vitamin D
Teriparatide is administered at a dose of 20 mcg/day as
if inadequate oral intake/ poor sunlight exposure. One
a subcutaneous injection. Because of the occurrence of
can consider BMD assessment if multiple risk factors/
osteosarcoma in rats treated with very high doses of
teriparatide, the duration of treatment recommended is 18months.
In case of males assess risk factors and secondarycauses. BMD should be done if there is history of
fragility fracture or secondary causes.
It has recently completed phase III clinical trials. It acts
(ii) Guidelines for patients with established
by inducing uncoupling in bone remodeling, increases
bone formation by increasing the replication of pre-osteoblasts into oseteoblasts, decreases bone resorption
Do complete evaluation with history / physical exam
by reducing the differentiation of pre-osteoclasts
and routine tests mentioned in medical evaluation
into osteoclasts and the bone resorbing activity of
above to establish the cause of osteoporosis.
osteoclasts, as a result increasing DXA measured bone
Do bone density every year to follow the treatment till
Consider bone markers (N-telopeptide and osteo-
Strontium Ranelate has shown to produce continuous
calcin) if needed to assess early changes during
increase in BMD at 3 years by 14.4% at lumbar spine, by
follow-up. These are particularly useful in steroid
8.3% at femoral neck and by 9.8% at total hip and bone
strength is directly related to bone mineral density. The
If metabolic parameters do not indicate significant
vertebral antifracture efficacy of Strontium Ranelate was
vitamin D deficiency, start treatment with specific
demonstrated with reductions in the relative risk of new
medication. In general bisphosphonates like
vertebral fractures by 49% after one year and by 41% after
alendronate / risedronate are the most powerful agents.
three years in postmenopausal women with osteoporosis
Risedronate may produce less GI intolerance.
and at least one vertebral fracture receiving daily oral
Although unproven in terms of fracture reduction,
Strontium (2 g/d) . Non vertebral fracture efficacy in
parenteral bisphosphonates like pamidronate and
postmenopausal women with osteoporosis is demonstrated
zolendronate are also options as they produce
by relative risk reduction of 16% for all non vertebral
Vol. 3, No. 2, June 2006
Raloxifene is a SERM, which provides multiple
benefits to women of postmenopausal age. Although
1. Jean-Yves Reginster, Pierre D Delmas. Prevention and
slightly less powerful than bisphosphonates, specially
treatment of postmenopausal osteoporosis, Rene
with regard to hip fracture reduction, it is a safe and
Rizzoli, Atlas of postmenopausal osteoporosis, Science
convenient option for many patients.
Limited role of HRT in light of recent studies. May be
2. B. Lawrence Riggs, A. Michael Parfitt. Drugs used to treat
used if menopausal symptoms predominate.
osteoporosis. The critical need for a uniformnomenclature based on their action on bone remodeling.
Consider combination therapy if no improvement after
3. Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D
status and its relationship with bone mineral density in
(iii) Guidelines for a patient with fracture due to
healthy Asian Indians. Osteoporosis international 2004;
Assess the site of fracture with X-ray.
4. Black DM, Cummings SR, Karpf DB, et al
trial of effect of alendronate on risk of fracture in women
Assess bone density but do not include the fracture
with existing vertebral fractures. Lancet 1996; 348: 1535
site (will give spuriously high results).
5. Gordon J Strewler. Decimal point - Osteoporosis therapy
at the 10 year mark. NEJM 2004 Mar; 350(12): 1172-1174.
Consider narcotics/ muscle relaxants if severe pain.
6. Harris ST, Watts NB, Genant HK, et al.
Consider calcitonin nasal spray 200 IU daily for 2-3
risedronate treatment on vertebral and non vertebral
months for analgesic effect. Higher doses can be used
fractures in women with post menopausal osteoporosis.
Start usual osteoporosis treatment in combination with
7. Kanatsu K, Aihara E, Okayama M, et al.
calcitonin. Teriparatide is the drug of choice.
associated with less GI irritation than Alendronate.
J Gastroenterol Hepatol 2004; 19(5): 512-250.
After 2-3 months start physical exercise program.
8. Ian R Reid, Jacques P Brown, Pierre J Munier, et al
Intravenous zoledronic acid in postmenopausal womenwith low bone mineral density. NEJM Feb 2002; 346(9):
As more anti-osteoporosis molecules become widely
available in India, it is imperative for physicians to select
9. Markowitz GS, Fine PL, Stack JI, et al.
Toxic acute tubular
appropriate therapy for their patients. The caveat in treating
necrosis following treatment with zoledronate (Zometa).
osteoporosis in India is the high prevalence of vitamin D/
calcium undernutrition. One should check the patient’s
10. Delmas PD, Recker RR, Chestnut, et al.
calcium and vitamin D axis, by estimating serum calcium,
significantly reduces fracture risk in postmenopausal
phosphorus, alkaline phosphatase levels, and, ideally, by
osteoporosis when administered daily or with a unique
estimating serum PTH and 25(OH) vitamin D levels too.
drug free interval. Osteoporosis Int 2002; 13(suppl 1):
Correction of abnormalities in these levels by judicious
use of calcium and vitamin D is desirable before initiating
11. Miller PD, McClung M, Macovei L, et al.
specific drug treatment. Failure to correct these
ibandronate therapy in postmenopausal osteoporosis:
abnormalities may not only result in poor response to drug
one year results from the Mobile study. JBMR 2005
therapy, but may actually have deleterious effects.
When deciding the treatment, aspects like individual
12. Ralph C, Schimmer, Frieder Bauss. Effect of daily and
intermittent use of Ibandronate on bone mass and bone
values, absolute risk of fracture, extraskeletal effects, and
turnover in post menopausal osteoporosis. Clin ther.
costs need to be considered. If the goal is to decrease risk
of vertebral fractures then the choices would includeraloxifene, calcitonin, strontium in mild cases and
13. Canley JA, Robbins J, Chen Z, et al.
Effects of estrogen
plus progestin on risk of fracture and bone mineral
risedronate, or alendronate in moderate to severe cases. If
density. The womens Health Intiative Randomized Trial.
the goal is to reduce the risk of vertebral and non vertebral
fractures then bisphosphonates like alendronate or
14. Ettinger B, Black DM, Mitlak BH, et al.
risedronate or ibandronate would be preferable. For those
vertebral fracture risk in post menopausal women with
with severe osteoporosis with pre existing fracture,
osteoporosis treated with Raloxifene; JAMA 1999; 282:
teriparatide would be a good option.
Vol. 3, No. 2, June 2006
15. Chestnut CH, Silverman S, Andrano K, et al.
Randomised trial of nasal spray salmon calcitonin in post
19. Marie PJ, Ammann P, Boivin G, et al.
menopausal women with established osteoporosis: the
action and therapeutical potential of strontium in bone.
PROOF study. Am J Med 2000; 109: 267-276.
Calcify tissue Int 2001; 69: 121-129.
16. Neer RM, Arnaud CD, Zanchetta JR, et al.
Effect of PTH
20. Meunier PJ, Roux C, Seeman E, et al.
The effects of
(1-34) on fractures and bone mineral density in post
Strontium Ranelate on the risk of vertebral fracture in
menopausal women with osteoporosis. N Eng J Med
women with postmenopausal osteoporosis. N Engl J Med
17. Bruce Ettinger, Javier San Martin, Gerald Crans, et al.
21. J Y Reginster, E Seeman, P J Meunier, et al.
Differential effects of Teriparatide on BMD after treatment
Ranelate reduces the risk of non vertebral fractures in
with Raloxifene or Alendronate. JBMR 2004 May; 19(5):
postmenopausal women with osteoporosis:Treatment of
peripheral osteoporosis study(TROPOS) study. J ClinEndocrinol Metab 2005; 90: 2816 2822.
18. F. Cosman, J Nieves, R Lindsay, et al
hormone added to established hormone therapy: Effects
22. D’Haese PC, Verberckmoes SC, Schrooten I, De Broe
on vertebral fracture and maintenance of bone mass after
ME. Strontium and chronic renal failure. Kidney 2000; 9:
parathyroid hormone withdrawal. JBMR May 2001; 16:
Vol. 3, No. 2, June 2006
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