09-Bernabei_- 25/11/14 17:21 Pagina 201
Mini-review
Screening, diagnosis and treatment of osteoporosis:
a brief review
Roberto Bernabei
Anna Maria Martone
Elena Ortolani
Francesco Landi
Emanuele Marzetti
Department of Geriatrics, Neurosciences and Orthopedics,
Catholic University of the Sacred Heart School of Medicine,
Rome, Italy
Address for correspondence:
Emanuele Marzetti, MD, PhD
Department of Geriatrics, Neurosciences and Orthopedics
Catholic University of the Sacred Heart School of Medicine
University Hospital “Agostino Gemelli”
Largo A. Gemelli 1
00168 Rome, Italy
Phone: +39 06 3015-5559 - Fax: +39 06 3051-911
E-mail: emarzetti@live.com
Summary
Osteoporosis is a highly prevalent condition character-
ized by decreases in bone mass and microarchitectural
alterations. Bone fractures, especially of the hip and ver-
tebrae, are the most burdensome complications of osteo-
porosis, being associated with high risk of disability, in-
stitutionalization and mortality. The detection of osteo-
porosis relies on the quantification of bone mineral densi-
ty via imaging techniques such as dual-energy X-ray ab-
sorptiometry. However, therapeutic decision-making
should be based on a comprehensive fracture risk as-
sessment, which may be obtained through validated algo-
rithms. Once the decision of treating has been taken, non-
pharmacological strategies should be implemented to-
gether with the prescription of anti-osteoporotic agents.
Numerous drugs are currently available to treat osteo-
porosis and the choice of a specific compound should be
guided by efficacy and safety considerations. The present
review provides a concise synopsis of the current evi-
dence in the management of osteoporosis, from screen-
ing to drug prescription. Novel anti-osteoporotic agents
are also briefly presented.
KEY WORDS: vitamin D; denosumab; bisphosphonates; teriparatide; strontium
ranelate.
Introduction
Osteoporosis is a bone disease characterized by a decrease
in bone mass and microarchitectural alterations which re-
Clinical Cases in Mineral and Bone Metabolism 2014; 11(3): 201-207
sults in bone fragility and increased risk of fractures. Accord-
ing to the World Health Organization (WHO), osteoporosis is
defined as a bone mineral density (BMD) at the hip and/or
the spine at least 2.5 standard deviations below the mean
peak bone mass of young healthy adults as determined by
dual-energy X-ray absorptiometry (DXA) (1).
The prevalence of osteoporosis rises steadily with advancing
age and is projected to increase substantially due to the de-
mographic transition occurring worldwide. Osteoporosis is
estimated to cause 1.5 million fractures annually in the Unit-
ed States (2). In Italy, approximately 3.5 million persons are
osteoporotic, with over 90.000 fractures yearly in those aged
50 years or older (3).
Mortality associated with osteoporotic fractures ranges from
15 to 30%, a rate similar to breast cancer and stroke (3).
Furthermore, 50% of women with osteoporotic hip fractures
develop disability, with significant impact on the capacity to
live independently and, in most cases, institutionalization (3).
Several risk factors have been identified for primary osteo-
porosis (Table 1). Secondary osteoporosis may be the con-
sequence of endocrine and metabolism disorders (e.g., hy-
pogonadism, hypercortisolism, hyperparathyroidism, hyper-
thyroidism, anorexia), lymphoproliferative disorders, intesti-
nal malabsorption conditions, rheumatoid arthritis, renal fail-
ure, collagenopathies, or certain drugs (e.g., corticosteroids,
selective serotonin reuptake inhibitors, anticoagulants and
antidiabetic medications) (3). Regardless of the etiology, in
all cases of osteoporosis an imbalance exists between bone
resorption and formation: the rate of bone formation is often
normal, whereas resorption by osteoclasts is increased (4).
However, the initiating event in the process of osteoclastic
activation is not yet completely understood.
Screening and diagnosis of osteoporosis
The presence of osteoporosis should be ascertained in all
women aged ≥ 65 years (2). Men ≥ 65 years or women aged
≤ 65 years should be screened for the presence of risk fac-
tors such as early menopause (≤ 45 years), anorexia, smok-
ing habit or alcohol abuse, chronic use of certain drugs or
diseases associated with an increased risk for osteoporosis
Table 1 - Major risk factors for primary osteoporosis.
Advancing age
Female sex
White or Asian race
Low body weight / body mass index
Family history of osteoporotic fractures
Early menopause
Sedentary lifestyle
Excessive alcohol (> 2 drinks per day), caffeine, and tobacco use
Low calcium and/or vitamin D intake
Inadequate sun exposure
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R. Bernabei et al.
(3). The first-line assessment includes the determination of
erythrocyte sedimentation rate, blood cell count, protein
electrophoresis, serum calcium, serum phosphorus, serum
alkaline phosphatase, serum creatinine, and 24-hour urinary
calcium excretion, in order to exclude possible causes of
secondary osteoporosis (3). Determination of bone turnover
markers is not recommended.
DXA is presently considered the gold standard imaging tech-
nique for the diagnosis of osteoporosis because it shows the
best predictive value for fracture risk (3). An estimate of frac-
ture risk may be obtained with DXA of radium, ulna, spinal
column or proximal femur. In persons aged ≥ 65 years DXA
should be performed at the proximal femur because os-
teoarthritis of the column may bias the results. Moreover,
BMD of the hip is a stronger predictor of future fracture risk
than spine BMD. As a general rule, the risk of fracture in-
creases 1.5-3 times each standard deviation of BMD below
the reference population (3). Normal BMD is indicated by a T
score of 1 to -1, whilst a T score ≥ -2.5 is diagnostic for os-
teoporosis. T score values between -1 and -2.5 identify a
condition known as osteopenia which is associated with low
to medium fracture risk, but frequent progression to osteo-
porosis. The correct identification and management of os-
teopenic subjects is a high-priority public health issue, if one
considers that approximately 35 million Americans suffer
from osteopenia (5).
The estimation of absolute risk of fractures and, therefore,
therapeutic decision-making should not be based solely on
BMD determination; rather, it requires a comprehensive eval-
uation of the patient, taking into account all of the known risk
factors for osteoporotic fractures. In this context, sensitive
tools have been developed which are routinely used in clini-
cal practice. Besides its role in the identification of osteo-
porosis, DXA is also useful to monitor the efficacy of specific
treatments. Roughly, 0.5-2% of bone mass is lost every year,
whilst anti-osteoporosis therapies allow gaining approximate-
ly 1-6% yearly. Since the least significant change of DXA is
2-4%, it is recommended to repeat it not earlier than 1-2
years from the beginning of treatment (3).
Therapeutic strategies against osteoporosis
Non-pharmacological treatments
Many strategies are available to prevent osteoporosis and its
complications, such as supplementation with calcium (500-
1,000 mg daily) and vitamin D, physical activity and multidis-
ciplinary interventions to decrease the risk of falls (5). These
premises also represent the basis for every specific pharma-
cological treatment, since calcium and vitamin D deficiency
is the most common cause of non-responsiveness to anti-os-
teoporotic medications.
Vitamin D supplementation
The major active metabolite of vitamin D, 1α,25-dihydroxy-
colecalciferol [1,25 (OH)2D3] derives for 80% from the con-
version of 7-dehydrocholesterol by UV light and 20% from
Table 2 - Vitamin D supplementation dosages.
Baseline 25 (OH)D levels Cumulative therapeutic dose of vitamin D
<10 ng/mL or 25 nmol/L 1,000,000
10-20 ng/mL or 25-50 nmol/L 600,000
20-30 ng/mL or 50-75 nmol/L 300,000
202
the diet, in particular blue fish and dairy products. The vita-
min D precursor is liposoluble and settles mostly in the adi-
pose tissue. The free quota is converted in the liver into 25-
hydroxycolecalciferol [25 (OH) D], the major circulating vita-
min D metabolite, whose levels are the most reliable index of
vitamin D status. 25 (OH) D is converted into the active
metabolite in the kidney, through a complex homeostatic
mechanism involving parathyroid hormone (PTH) and calci-
um and phosphorus serum levels (6).
Vitamin D receptors are ubiquitous and are especially abun-
dant in osteoblasts, chondrocytes, hepatocytes, parathyroid
cells, and muscle cells (6). Vitamin D promotes cell prolifera-
tion and differentiation by a genomic pathway (7, 8). Vitamin
D also acts via a non-genomic mechanism to modulate cell
responses to various stimuli (7, 8). The major actions of vita-
min D in the context of bone homeostasis include the regula-
tion of calcium metabolism by increasing intestinal absorption
and renal reabsorption, and the stimulation of the synthesis of
bone proteins such as osteocalcin by osteoblasts (9).
The daily vitamin D allowance ranges from 1,500 IU (healthy
adults) to 2,300 IU (elderly with low calcium intake). Since
the average Mediterranean diet provides around 300 IU per
day, subjects with insufficient sun exposure should receive
1,200-2,000 IU vitamin D daily (10-12).
In Italy, approximately 50% of young healthy individuals
show vitamin D insufficiency [i.e., serum 25(OH)D levels 20-
30 ng/mL] during the winter season (13). The prevalence of
vitamin D deficiency [i.e., serum 25(OH)D levels < 20 ng/mL]
increases with advancing aging, affecting virtually all non-
supplemented elderly subjects (14). As such, individuals
aged 70 years or older should be considered vitamin D insuf-
ficient unless they pursue a lifestyle characterized by exten-
sive sun exposure (15). It is therefore recommended to pre-
scribe older adults with vitamin D supplementation (800 per
day) as a primary prevention measure (Table 2) (15).
If vitamin D deficiency is detected, a cumulative dose of
300,000-1,000,000 IU over 1-4 weeks is recommended, fol-
lowed by a maintenance dose of 800-2.000 IU/day (or week-
ly/monthly equivalent) (15). The dosage should be based on
age, degree of sun exposure, and baseline 25(OH) D levels
(Table 2). In subjects persistently at risk for deficiency, it is
recommended to check vitamin D serum concentration after
3-6 months from the beginning of the supplementation regi-
men (15). Finally, vitamin D supplementation should be care-
fully monitored in patients at risk of vitamin D intoxication
(granulomatosis) or with primary hyperparathyroidism (15).
Physical activity
Physical activity is highly effective in attenuating the age-re-
lated bone mass loss (16, 17). It is therefore recommended
to carry out a minimum of activity (for example, 30 minutes
of walk daily) for its positive effects on bone mass and the
risk of falling (18).
Comprehensive interventions on the risk of falls
Exercises for muscle strengthening and gait training have
shown to reduce the risk of falls and related injuries in elder-
Daily maintenance dose
2,000
1,000
800
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Screening, diagnosis and treatment of osteoporosis: a brief review
ly subjects (18). Psychotropic drugs (e.g., benzodiazepines,
antipsychotics, and antidepressant) should be avoided
whenever possible or used with extreme caution. Adequate
measures should finally be taken to avoid falls at home (e.g.,
handrails on stairs and handholds in the bathroom).
Pharmacological treatments
Treatment threshold
BMD as estimated by DXA does not suffice to start an anti-
osteoporotic treatment. As previously mentioned, a compre-
hensive assessment is necessary to quantify long-term frac-
ture risk (18). In fact, pharmacological treatments are aimed
at individuals who are already osteoporotic and therefore at
risk of osteoporotic fractures or re-fractures.
In the literature various instruments are described to esti-
mate the 10-year fracture risk. One of the most popular is
the “Derived fracture Risk Assessment” or “DeFRA” which in-
cludes a number of risk factors, such as family history of hip
fracture, smoking, use of immunosuppressant drugs, hyper-
thyroidism, alcohol abuse, previous vertebral or femoral frac-
ture, rheumatoid arthritis or other autoimmune diseases (19).
Individuals at high risk for fractures, as indicated by DeFRA
or other similar algorithms, are candidate for treatment re-
gardless of BMD values.
Drugs
Pharmacological agents against osteoporosis either de-
crease bone resorption to produce secondary gains in bone
mass or directly stimulate increases in bone mass (20). A
brief overview of the main drugs currently available to treat
osteoporosis is provided in the following subsections.
Bisphosphonates
Bisphosphonates are sintetic compounds with anti-resorptive
activity (21). They act on bone through binding to hydroxyap-
atite and inhibiting osteoclast activation. Bisphosphonates
possess high affinity for bone and little effect on other organ
systems. Pharmacokinetics of bisphosphonates explain their
overall good tolerability. Bisphosphonates have a poor in-
testinal absorption and therefore show low plasma levels af-
ter oral administration (21). Circulating levels of bisphospho-
nates quickly decrease due to fast adhesion to bone surface,
so that the plasma half-life is very short, contrary to the half-
life of bisphosphonate depots in the bone which is probably
up to 10 years or longer (21). Bisphosphonates currently
registered in Europe for the treatment of osteoporosis in-
clude alendronate, clodronate, etidronate, ibandronate, rise-
dronate, and zoledronate. Several formulations bisphospho-
nates are available for the management of osteoporosis
(e.g., oral and intravenous formulations, with weekly monthly
and annual dosing schedules). Dosing convenience is a key
element in the long-term management of a chronic disease.
Studies performed to assess adherence with once-monthly,
once-weekly or once-daily dosing suggest that adherence
with either weekly or monthly dosing is significantly better
than with once-daily formulations (22).
All approved bisphosphonates have shown to decrease bone
turnover in a dose-dependent manner (21). While all bispho-
sphonates reduce vertebral fracture risk and increase BMD,
only some of them are effective at reducing the risk for non-
vertebral and hip fractures (21).
Gastrointestinal side effect are quite common and can be
partially prevented by instructing the patient on how to take
the drug (21). Also, weekly or monthly formulations decrease
Clinical Cases in Mineral and Bone Metabolism 2014; 11(3): 201-207
the probability of repeated stresses to the gastro-esophageal
mucosa (23-28). Acute phase response (APR) is a transient
flu-like syndrome, usually lasting 2-3 days, that develops in
30% of patients after the first intravenous administration of
amino-bisphosphonates (29). It is associated with a rapid re-
duction of circulating lymphocites and increases in serum
levels of C-reactive protein. APR can be prevented or man-
aged with paracetamol or non-steroidal anti-inflammatory
drugs (30).
Atypical femoral subtrochanteric/diaphyseal fractures have
been described in patients under long-term biphosphonate
treatment, particularly in those receiving glucocorticoids
and/or another anti-resorptive medication (31-35). Atypical
femoral fractures develop spontaneously or after a minimal
trauma. Additional studies are needed to determine the
mechanisms underlying these fractures and the characteris-
tics of patients at risk for them.
Treatment with bisphosphonates has been associated with
higher risk of atrial fibrillation in some (36-38) but not all
studies (39, 40). In 2011, the Food and Drug Administration
(FDA) has concluded that there were not enough reasons to
suspect that treatment with bisphosphonates could induce
atrial fibrillation. Moreover, a reduced risk of myocardial in-
farction was recently observed during bisphosphonate treat-
ment in patient with rheumatoid arthritis (41).
Osteonecrosis of the jaw (ONJ) is a rare event in patients
treated with bisphosphonates and the level of evidence and
prediction of risk factors are relatively low (42). From a
pathological point of view, ONJ consists in a chronic os-
teomyelitis caused by germs of the oral flora, in particular
actinomyces (43). However, the pathogenesis of ONJ has
not yet been clearly defined. The main risk factors for ONJ
include prolonged treatment with oral bisphosphonates, cor-
ticosteroid therapy or immunosuppressive agents. Tooth ex-
traction and dental and periodontal diseases are the main
predisposing factors (44, 45). Cases of ONJ have been de-
scribed also in subjects who have never been treated with
bisphosphonates (43).
Musculoskeletal pain, usually reversible after discontinuation
(46, 47), ocular inflammation (48), urticaria (49), or mucositis
(50) have rarely been reported after use of bisphosphonates.
Denosumab
Denosumab is a human monoclonal antibody that blocks the
interaction of receptor activator of nuclear factor kB ligand
(RANKL) with receptor activator of nuclear factor kB (RANK),
whereby inhibiting bone resorption strongly and rapidly (51).
In postmenopausal women with low BMD, denosumab ad-
ministered subcutaneously 60 mg every 6 months increased
BMD by 1 to 7% depending on the skeletal site (51). The in-
creases in BMD are higher than those obtained with the
more potent bisphosphonates (51). In postmenopausal os-
teoporotic women, denosumab decreased the risk of verte-
bral and non-spine fractures by 70% and 20%, respectively
(52). Denosumab slowed bone turnover also in older men re-
ceiving androgen-deprivation therapy for prostate cancer, in-
creasing BMD by 4 to 7% as well as decreasing the inci-
dence of vertebral fractures by 60% and the incidence of
multiple fractures by 70% (53).
An association with ONJ has been observed in denosumab
registration trials, although the event appears to be extreme-
ly rare (6 cases/4450 patients) (54). The pathogenesis of this
side effect has not yet been clearly defined, but it seems rea-
sonable to equate denosumab to bisphosphonates in this re-
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R. Bernabei et al.
gard. Cases of atypical femoral subtrochanteric/diaphyseal
fractures similar to those reported in patients treated with
bisphosphonates have been described in women with post-
menopausal osteoporosis treated with denosumab (55-57).
The length of exposure to denosumab at the time of atypical
fracture diagnosis was longer than 2.5 years. Based on data
from the FREEDOM study, the incidence of atypical fractures
is extremely low (1 case/4450 patients) (54). However, no re-
liable estimates can be given based on available data.
Hormone replacement therapy (HRT)
Treatment of osteoporotic women with HRT to prevent frac-
tures has been a long-standing controversial issue. Estrogen
replacement, alone or in combination with tibolone (a syn-
thetic steroid with estrogenic and androgenic properties), in-
creases bone mass (58). The Women’s Health Initiative trial
showed that the incidence of osteoporotic fractures was re-
duced by 24%, with a 34% risk reduction for hip and verte-
bral fractures (58). However, long-term side effects, in partic-
ular the development of breast cancer, risks of cardiovascu-
lar events and thromboembolism, limit the use of HRT as a
countermeasure to osteoporosis. HRT is indeed no longer
recommended for the prevention and treatment of post-
menopausal osteoporosis.
Selective estrogen receptor modulators (SERMs)
SERMs are synthetic molecules that bind to the estrogen re-
ceptor thereby acting as estrogen agonists on bone and liver
and as antagonists on breast and genitor-urinary tract.
Raloxifene at the dose of 60 to 120 mg daily increases BMD
by 2 to 3% at the lumbar spine and femoral neck (59, 60).
Based on data from the MORE study, raloxifene reduces the
incidence of vertebral fractures by 40 to 50%, with no effect
on non-vertebral fractures (61). Raloxifene also reduces the
risk of estrogen receptor-positive breast cancer, whilst the
impact on cardiovascular risk is controversial (62-65).
Bazedoxifene at the dose of 20 to 40 mg daily decreases
bone turnover markers, while increasing BMD of the lumbar
spine by 2% and preventing bone loss at the hip (66, 67). In
postmenopausal osteoporotic women, bazedoxifene de-
creases the risk of vertebral fractures by 40% of non-verte-
bral fracture in high-risk patients (67).
Major concerns regarding side effects of SERMs are related to
an increased risk of thrombotic and thromboembolic events.
Overall, the size of this side effect is comparable to what is
observed during HRT (68). The incidence of thrombotic events
is higher during the first 2 years of treatment, and progressive-
ly decreases thereafter (69). Hence, SERMs should not be
prescribed or the treatment stopped in individuals at risk for
thromboembolism (i.e., bedridden patients). An increased risk
for fatal stroke has also been reported in postmenopausal
women over 5.6 years of follow-up (70). Less relevant side ef-
fects associated with SERMs include worsening of post-
menopausal symptoms such as leg cramps or vasomotor in-
stability, especially at the beginning of treatment (71).
Recombinant human PTH
Recombinant 1-34 fragment of human PTH − rhPTH(1-
34)teriparatide − and recombinant human intact PTH − rh-
PTH(1-84) − stimulate bone remodeling by inducing an in-
crease in bone formation followed by a slower increase in
bone resorption (72). They strongly increase BMD in the tra-
becular compartment, whereas their effect appears lower
than bisphosphonates in the cortical sites.
204
In osteoporotic women with prevalent vertebral fractures, rh-
PTH decreases the incidence of new vertebral fractures by
65% and non-vertebral fractures by 53% (72). The best can-
didates for teriparatide and rhPTH(1-84) treatment are pa-
tients with pre-existing osteoporotic fractures, patients with
very low BMD and those with unsatisfactory response to anti-
resorptive therapy. The effects of the combination therapy
with rhPTH(1-84) and alendronate on BMD are controversial,
with some authors reporting no synergy (73), while others
found an additive effect (74). However, according to guide-
lines, the combined treatment with recombinant PTH and bis-
phosphonates should not exceed 24 months (74). The safety
profile of teriparatide is overall good. A transient increase in
serum calcium levels and calcium renal excretion without
clinical manifestation has been reported. Absolute contraindi-
cations to teriparatide include primary hyperparathyroidism,
Paget’s disease of bone, previous radiation therapy of the
skeleton and primary or metastatic bone cancer (20).
Strontium ranelate (SR)
SR is adsorbed onto the bone surface and increases bone
strength by being incorporated in a dose-dependent manner
into bone tissue to change the crystal structure without af-
fecting mineralization (75). SR increases bone formation
markers, reduces bone resorption markers and increases
BMD progressively and dose-dependently (76, 77). In post-
menopausal osteoporotic women during long term treatment
(4 years), SR decreased the incidence of vertebral fractures
by 33% (78). SR also decreases the incidence of non-verte-
bral fractures by about 15% and even more (31%) in the old-
est women (79, 80). The European Medicines Agency (EMA)
Committee for Medicinal Product for Human Use (CHMP)
recommended SR only be used for the treatment of severe
osteoporosis in men and postmenopausal women at high
risk of fracture (81).
The most common side effects of SR therapy are nausea
and diarrhea which usually develop at the beginning of the
treatment and generally disappear after 3 months of therapy.
Albeit rarely, SR administration has been associated with se-
vere, potentially lethal, skin reactions, such as drug reaction
with eosinophilia and systemic symptoms (DRESS),
Stevens-Johnson syndrome and toxic epidermal necrolysis
(82-85).
Recently, the EMA warned against a possible association
between the use of SR and cardiovascular events, above all
myocardial infarction (86). SR is therefore contraindicated in
patients with history of cardiovascular disease or uncon-
trolled hypertension. In addition, it is recommended patients
be evaluated for cardiovascular risk before starting treatment
with SR and at regular intervals during treatment. The possi-
ble association between SR and venous thromboembolism
(VTE) makes the drug contraindicated also in patients with
current VTE or a history of VTE, as well as in those who are
temporarily or permanently immobilized (87). Taking all this
into account, SR is not a first-choice option in older osteo-
porotic patients (88).
Other “non-hormonal” drugs and novel therapeutic agents
A number of drugs with beneficial effects on bone metabo-
lism and calcium-phosphorous homeostasis include calci-
tonin, ipriflavone, and thiazide diuretics. However, none of
these agents is currently recommended for osteoporosis
treatment because either ineffective or not supported by ad-
equate evidence.
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Screening, diagnosis and treatment of osteoporosis: a brief review
Research into anti-osteoporotic therapeutics has led to the
discovery of new candidate drugs. For instance, odanacanib
acts as a selective inhibitor of cathepsin K, an osteclast-de-
rived protease that degrades bone collagen. This property
makes odanacanib an alternative anti-resorptive drug (89).
Indeed, odanacanib provided incremental BMD gains in os-
teoporotic women under alendronate treatment (89). Anoth-
er compound, tert-butyl 4-[3-(1H-indole-2-carboxamido)
benzoyl]piperazin-e-1-carboxylate (OA10), inhibits RANKL-
mediated osteoclast formation and osteoclastic bone re-
sorption in a dose-dependent manner (90). Similarly,
C(25)H(32)N(4)O(4)S(2) (NecroX-7) inhibits osteoclast dif-
ferentiation by suppressing nuclear factor κB activity and c-
Fos expression (91). Pharmacological inhibition of scle-
rostin, a negative regulator of bone formation, may repre-
sent another potential approach to the treatment of osteo-
porosis by promoting bone anabolism (92).
Conclusion
The escalating prevalence of osteoporosis and its burden-
some clinical correlates urge health professionals to aban-
don the old notion of osteoporosis as a mere “natural
byproduct” of aging. Rather, the medical community is called
to promote an adequate awareness on the subject and put in
place large-scale screening and diagnostic procedures in or-
der to identify people with osteoporosis or at risk of develop-
ing the condition. This would allow the early correction of risk
factors for osteoporosis and the prompt institution of anti-os-
teoporotic treatments. In this regard, it needs to be consid-
ered that therapeutic decision-making should be based not
solely on BMD, but on comprehensive fracture risk assess-
ments. A relatively large number of medications is currently
available. Each drug (or class of drugs) possesses specific
advantages and side effects and should therefore be pre-
scribed or avoided in selected patient populations. New and
potentially highly effective agents are currently under devel-
opment which may offer novel therapeutic tools to counteract
what has rightly been called the osteoporosis epidemic.
Acknowledgements
This work was partly supported by the “Centro Study Achille
e Linda Lorenzon”. The Authors apologize to those re-
searchers whose excellent work could not be cited due to the
vast literature on the subject and space limitations.
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