REVIEW

Drug-induced Osteoporosis: Mechanisms and

Clinical Implications
Gherardo Mazziotti, MD, PhD,a Ernesto Canalis, MD,b,c Andrea Giustina, MDa
a
Department of Medical and Surgical Sciences, University of Brescia, Montichiari, Italy; bDepartment of Research, Saint Francis
Hospital and Medical Center, Hartford, Conn; cUniversity of Connecticut School of Medicine, Farmington.

ABSTRACT

Drug-induced osteoporosis is common and has a significant impact on the prognosis of patients suffering
from chronic debilitating diseases. Glucocorticoids are the drugs causing osteoporotic fractures most
frequently, but osteoporosis with fractures is observed also in women treated with aromatase inhibitors for
breast cancer, in men receiving anti-androgen therapy for prostate cancer, in postmenopausal women
treated with high doses of thyroxine, and in men and women treated with thiazolinediones for type 2
diabetes mellitus. Bone loss with fractures also occurs in patients treated with drugs targeting the immune
system, such as calcineurin inhibitors, antiretroviral drugs, selective inhibitors of serotonin reuptake,
anticonvulsants, loop diuretics, heparin, oral anticoagulants, and proton pump inhibitors.
© 2010 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2010) 123, 877-884

KEYWORDS: Drugs; Fractures; Osteoporosis; Secondary osteoporosis

Osteoporosis is a skeletal disorder characterized by a de-
crease in bone mineral density (BMD) and loss of structural
and biomechanical properties of the skeleton, leading to an
increased risk of fractures. Individual patients have genetic
and acquired risks for osteoporosis. Among acquired risks,
pharmacological interventions are important contributors to
the bone loss observed in osteoporosis (Table 1). Drug-
induced osteoporosis is common, and has a significant im-
pact on the morbidity and mortality of patients suffering
from chronic debilitating diseases for which drug interven-
tion is necessary. Unfortunately, awareness of this form of
Funding: This work was supported by MIUR and Centro di Ricerca
sull’Osteoporosi-University of Brescia/EULO (A. Giustina).
Conflict of Interest: Dr. Mazziotti has nothing to declare. Dr. Canalis
reports receiving consulting or lecture fees from Eli Lilly, GlaxoSmithKline,
Novartis, and Amgen. Dr. Giustina reports receiving consulting or lecture
fees from Abiogen, Eli Lilly, GlaxoSmithKline, Merck, Amgen, and
Stroder. No pharmaceutical industry funds were received for the prepara-
tion of the manuscript or related research.
Authorship: Each author has participated in the writing of the manu-
script and has seen and approved the submitted version. Further, each
author has been involved in the conception and design of the study and the
analysis of the data.
Requests for reprints should be addressed to Andrea Giustina, MD,
Department of Medical and Surgical Sciences, University of Brescia, c/o
Endocrinology Service, Montichiari Hospital, Via Ciotti 154, Montichiari
25018, Italy.
E-mail address: a.giustina@libero.it
secondary osteoporosis is limited. This article reviews the
mechanisms and clinical implications of drug-induced os-
teoporosis (Tables 2 and 3).
We performed a formal search of the electronic literature
(MEDLINE) from 1990 to 2009 using the following search
terms: osteoporosis, bone fractures and glucocorticoids, thy-
roxine, aromatase inhibitors, ovarian suppressing agents,
androgen deprivation therapy, thiazolidinediones, selective
serotonin reuptake inhibitors, anticonvulsants, heparins,
oral anticoagulants, loop diuretics, calcineurin inhibitors,
antiretroviral therapy, proton pump inhibitors. One hundred
and eighty-nine original articles, systematic reviews, and
meta-analyses from studies in humans published in the
English language were considered.
HORMONAL THERAPY
Glucocorticoids
Glucocorticoids are used in the treatment of inflammatory
and autoimmune diseases, neoplasias, and following organ
transplantation. Glucocorticoid-induced osteoporosis is the
most common form of secondary osteoporosis. The central
mechanism of action of glucocorticoids is decreased bone
formation, secondary to impaired osteoblastic differentia-
tion and function.1 However, during the initial phases of
glucocorticoid exposure, bone resorption is increased, ex-

0002-9343/$ -see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2010.02.028
878 The American Journal of Medicine, Vol 123, No 10, October 2010

plaining an early bone loss.2 Glucocorticoids inhibit bone for- porotic fractures remains increased in patients undergoing
mation and have additional indirect effects on bone metabo- cyclic corticosteroid treatment at high doses. It is noteworthy
lism, explaining an increased risk of fractures (for a complete that fracture risk decreases after discontinuation of oral corticoste-
review, see ref. 1). The underlying disorder for which glu- roids, although the time it takes to reduce the risk appears to
cocorticoids are administered is often associated with bone loss be variable.4 The risk of osteoporosis associated with in-
as a consequence of chronic inflam- haled glucocorticoids or with
mation, malnutrition, and reduced budesonide, a topical steroid used
physical activity.1 in inflammatory bowel disease, is
CLINICAL SIGNIFICANCE
Glucocorticoid-induced osteo- small because their absorption is
porosis is characterized by low ● Hormonal and nonhormonal (psycho- limited.
bone turnover and fractures, tropic and cardiovascular) drugs may In glucocorticoid-induced osteo-
which occur in 30%-50% of pa- cause osteoporosis. porosis, fractures occur at higher
tients.2 Glucocorticoids affect pre- BMDs than in postmenopausal osteo-
dominantly cancellous bone, in- ● Drug-induced osteoporosis occurs pri- porosis.5 Consequently, guidelines for
creasing the risk of vertebral marily in postmenopausal women, but the treatment of postmenopausal
fractures, which may be asymp- premenopausal women and men are also osteoporosis are not applicable to
tomatic and occur early during the significantly affected. glucocorticoid-induced osteoporo-
first months of glucocorticoid sis, and patients should be treated
● Glucocorticoids are the most common
treatment.2,3 Published reports at BMD T-scores of ⱕ⫺1.0 to
suggest that there is no dose of cause of drug-induced osteoporosis. ⫺1.5.6 Because vertebral fractures
glucocorticoid therapy that is safe ● Diagnostic criteria for postmenopausal may be asymptomatic, a radiolog-
for the skeleton. Regimens of osteoporosis do not necessarily apply to ical evaluation is often necessary
daily prednisone at doses as low drug-induced osteoporosis. for their identification.
as 2.5 mg have been associated It is appropriate to treat indivi-
with an increased risk of hip and ● Anti-osteoporotic treatments may be duals exposed to glucocorticoids
vertebral fractures. The risk in- effective in drug-induced osteoporosis, (prednisone equivalents ⱖ5 mg/day)
creases by 5-fold, with prednisone if drug discontinuation is not feasible. for 3-6 months. Vitamin D and cal-
doses above 7.5 mg daily. A dra- cium are recommended for the
matic 17-fold increase in vertebral management of all patients treated
fracture incidence was observed in with glucocorticoids. Bisphospho-
subjects who used prednisone continuously more than 10 nates should be considered for the prevention and treatment
mg per day for longer than 3 months. As expected, the of this disorder, because they can prevent the initial loss of
greatest increase in fracture incidence was seen in post- bone mass in this disorder. Alendronate, risedronate, and
menopausal females and elderly males. The risk of osteo- zoledronic acid were shown to prevent and reverse the loss
of BMD in glucocorticoid-induced osteoporosis with
greater effects than those observed with vitamin D and
Table 1 Drugs Associated with Osteoporosis calcium.7,8 In fact, bisphosphonates induce improvement of
BMD that is 2-fold greater than that observed during vita-
Hormonal therapy min D treatment (ie, 4.6% vs. 2.0%).8 Anabolic therapy
Glucocorticoids appears to be ideal for the treatment of glucocorticoid-
Thyroid hormone induced osteoporosis, and teriparatide causes a greater in-
Aromatase inhibitors
crease in BMD than alendronate and greater reduction in the
Ovarian suppressing agents
Androgen deprivation therapy
risk of vertebral fractures.9
Thiazolidinediones
Psychotropic and anticonvulsant therapy Thyroxine
Selective serotonin reuptake inhibitors Thyroxine is prescribed for the treatment of hypothyroid-
Anticonvulsants ism, goiter, and thyroid carcinoma following thyroid abla-
Drugs used for cardiovascular diseases tion. Patients with thyroid carcinoma are treated with high
Heparins doses of thyroxine to suppress endogenous thyrotropin
Oral anticoagulants (TSH). In hypothyroidism, thyroid replacement therapy is
Loop diuretics used to normalize serum thyroid hormone levels. However,
Drugs targeting the immune system about 25% of these patients are over-treated and display
Calcineurin inhibitors
suppressed serum levels of TSH.10 Subclinical thyrotoxico-
Anti-retroviral therapy
Drugs used for gastrointestinal diseases
sis causes atrial fibrillation, cardiac dysfunction, and bone
Proton pump inhibitors loss in elderly subjects and postmenopausal women.11 Thy-
roid hormones increase bone resorption directly and indi-
rectly by inducing the production of bone-resorbing cyto-
Mazziotti et al Drugs and Osteoporosis 879

Table 2 Mechanisms of Drug-induced Osteoporosis in Vivo

Effects on Bone Remodeling Effects on Calcium Metabolism

Bone Resorption Bone Formation Vitamin D Levels or Action PTH Secretion
Glucocorticoids 1 2 2 ↔
Thyroid hormone 1 1 ↔ ↔
Aromatase inhibitors 1 1 Not determined 2
Ovarian suppressing agents 1 1 2 Not determined
Androgen deprivation therapy 1 1 ↔ ↔
Thiazolidinediones ↔ 2 ↔ ↔
Selective serotonin reuptake inhibitors Not determined 2 Not determined Not determined
Anticonvulsants 1 1 2 1
Heparin 1 2 Not determined Not determined
Oral anticoagulants Not determined 2 Not determined Not determined
Loop diuretics 1 1 2 1
Calcineurin inhibitors 1 1 2 1
Anti-retroviral therapy 1 2 2 1
Proton pump inhibitors 1 1 2 1
PTH ⫽ Parathyroid hormone.
1 ⫽ increased; 2 ⫽ decreased; ↔ ⫽ unchanged.

kines.12 Recently, TSH was reported to inhibit bone
resorption directly, suggesting that the suppression of TSH
itself may cause bone loss.13,14
Thyrotoxicosis increases bone turnover, decreases BMD,
and increases the risk of fractures. The impact of subclinical
hyperthyroidism on the skeleton is dependent on the age and
sex of patients, duration of thyroxine treatment, and the
presence of additional factors predisposing them to bone
loss.11,15 Thyroid suppression therapy causes bone loss in
postmenopausal women, increasing the risk of vertebral and
hip fractures by 3- to 4-fold.11,15,16 There are no specific
guidelines for the prevention of bone loss when thyroid
suppression is necessary. Supplemental calcium and vita-
min D should be used, and patients with increased fracture
risk should be treated with antiresorptive drugs. However,
long-term TSH-suppressive therapy with thyroxine may re-
duce the beneficial effects of bisphosphonates on BMD.17

Table 3 Clinical Aspects of Drug-induced Osteoporosis: Aromatase Inhibitors

Impact on Bone Mineral Density and Fractures
Aromatase inhibitors are more effective than tamoxifen as
Bone adjuvant therapy of estrogen-receptor-positive breast can-
Mineral cer, with longer disease-free survival and without the risk of
Density Fractures endometrial hyperplasia and cancer, cerebrovascular and
Lumbar venous thromboembolic events. Whereas tamoxifen can
Spine Hip Vertebral Nonvertebral have estrogen-like effects on bone, aromatase inhibitors
Glucocorticoids 2 2 1 1 induce bone loss. Aromatase inhibitors inhibit the aromati-
Thyroid hormone 2 2 1 1 zation of androgens and their conversion to estrogens in
Aromatase inhibitors 2 2 1 1 peripheral tissues. The substantial reduction in estrogen
Ovarian suppressing agents 2 2 1 1 concentrations caused by the suppression of androgen aro-
Androgen deprivation 2 2 1 1 matization causes bone loss. Anastrazole and letrozole are
therapy nonsteroidal aromatase inhibitors, and exemestane is a ste-
Thiazolidinediones 2 2 1 1
roid similar to androstenedione that binds and irreversibly
Selective serotonin 2 2 ↔* 1
reuptake inhibitors inhibits aromatase.
Anticonvulsants 2 2 ↔* 1 Letrozole and anastrozole increase bone turnover, de-
Heparin 2 2 1 Not determined crease BMD, and increase the relative risk of vertebral and
Oral anticoagulants ↔ ↔ 1 ↔1 nonvertebral fractures by 40%, when compared with tamox-
Loop diuretics ↔2 2 ↔1* 1 ifen.18,19 The skeletal effects observed are correlated in-
Calcineurin inhibitors 2 2 1 1 versely with baseline BMD and serum estradiol concentra-
Anti-retroviral therapy 2 2 1 1 tions, and osteoporosis is more prevalent in women starting
Proton pump inhibitors 2 ↔ 1 1
aromatase inhibitors early after menopause.19,20 There is
1 ⫽ increased; 2 ⫽ decreased; ↔ ⫽ unchanged. only a partial recovery of BMD following the withdrawal of
*Fractures were assessed by a clinical approach.
aromatase inhibitors. Bone loss with increased risk of fra-
880
gility fractures also is observed in women receiving
exemestane.21
Zoledronic acid and risedronate were shown to prevent
and reverse aromatase inhibitor-induced bone loss, but data
on fracture reduction efficacy are scanty.22,23 Zoledronic
acid was more effective in preventing than in reversing bone
loss, and as an additional benefit, it increased disease-free
survival in subjects with carcinoma of the breast.22,24 De-
nosumab, a monoclonal antibody against receptor activator
of nuclear factor– kappa B ligand, is effective in preventing
aromatase inhibitor-induced bone loss in women with non-
metastatic breast carcinoma.25 Patients should receive sup-
plemental calcium and vitamin D. Bisphosphonates should
be prescribed to individuals with fractures, established os-
teoporosis (T score ⱕ⫺2.5) or osteopenia (T-score between
⫺1 and ⫺2.5 SD), and additional risk factors.26 Women
with normal BMD and without osteoporosis risk factors
should be monitored with dual-energy X-ray absorptiometry
every 12 to 24 months, although fragility fractures may
occur independently of BMD.
Ovarian Suppressing Agents
Gonadotropin-releasing Hormone Agonists. Gonadotro-
pin-releasing hormone agonists are drugs with increased
receptor affinity or prolonged half lives, leading to persis-
tent activation of gonadotropin-releasing hormone recep-
tors, causing an initial release of pituitary gonadotropins
followed by a downregulation of gonadotropin-releasing
hormone receptor and suppression of gonadotropin secre-
tion. Consequently, ovarian sex-steroid production is sup-
pressed. Gonadotropin-releasing hormone agonists are ef-
fective in the management of endometriosis and breast
cancer in premenopausal women. They suppress estrogen
levels and cause bone loss. A decrease of about 6%/year in
BMD is observed in patients on gonadotropin-releasing
hormone agonists with a recovery of bone mass after dis-
continuation. Gonadotropin-releasing hormone agonists
may not increase the risk of fragility fractures in women
with normal BMD.27
Medroxyprogesterone Acetate. Medroxyprogesterone ac-
etate inhibits gonadotropin secretion, suppressing ovulation
and production of estrogens by the ovary. It is effective in
the treatment of endometriosis and as a contraceptive agent.
Medroxyprogesterone acetate causes a decrease in BMD
and increases the risk of fractures. Its discontinuation results
in BMD restoration.28,29
Androgen Deprivation Therapy
Androgen deprivation therapy is used in the treatment of
metastatic and locally advanced prostate carcinoma, and is
effective in reducing tumor growth and improving survival
of men affected by this tumor. Androgen deprivation ther-
apy is achieved with gonadotropin-releasing hormone ana-
logs alone or in combination with anti-androgenic therapy.
Gonadotropin-releasing hormone analogs reduce serum tes-
The American Journal of Medicine, Vol 123, No 10, October 2010
tosterone and estradiol levels and increase bone turnover
and bone loss.30 Decrease in lean body mass, increase in fat
mass, and impaired muscular strength are observed and may
contribute to increased risk of fractures.31
In men with carcinoma of the prostate, BMD at hip,
ultradistal radius, and lumbar spine decreases by 2%-5%
after 12 months of androgen deprivation therapy, and the
relative risk of vertebral and hip fractures increases by
40%-50%.32,33 The risk of fractures correlates with the
degree and rate of BMD decrease, patient age, and duration
of therapy, but not with tumor stage.33,34
Treatment is recommended for patients with pre-existing
osteoporotic fractures, T-scores ⱕ⫺2.5 or between ⫺1 and
⫺2.5 with significant risk factors for fractures.35 Calcium
and vitamin D are indicated. Bisphosphonates are effective
in the prevention and reversal of androgen deprivation ther-
apy-induced bone loss, but data on fracture reduction effects
are scanty.36,37 Selective estrogen receptor modulators, such
as raloxifene and toremifene, also have beneficial effects on
BMD.38,39 Recently, denosumab was shown to prevent bone
loss and the incidence of vertebral fractures in men receiv-
ing androgen deprivation therapy.40 An assessment of risk-
benefit ratio of androgen deprivation therapy should be
performed. Indeed, androgen deprivation therapy is fre-
quently administered to patients with nonmetastatic prostate
cancer, in whom effects on survival have not been docu-
mented. Alternatives to androgen deprivation therapy, such
as the nonsteroidal anti-androgen bicalutamide, may be
preferable in the management of prostate carcinoma in pa-
tients with osteoporosis because this drug has comparable
effectiveness to gonadotropin-releasing hormone agonists
without deleterious effects on bone.41
Thiazolidinediones
Thiazolidinediones are insulin-sensitizing drugs used for the
treatment or prevention of type 2 diabetes mellitus. Thiazo-
lidinediones may cause side effects on the cardiovascular
system, liver and skeleton. Currently available thiazo-
lidinediones, rosiglitazone and pioglitazone, are selective
agonists of peroxisome proliferator-activated receptor-␥. In
vitro and in vivo studies demonstrate that peroxisome pro-
liferator-activated receptor-␥ induction in mesenchymal
cells leads to increased adipogenesis and decreased osteo-
blastogenesis.42 Thiazolidinediones also decrease the ex-
pression of insulin-like growth factor I, and this may con-
tribute to decreased bone formation.43 In addition,
thiazolidinediones promote osteoclast differentiation and
bone resorption.44
Long-term treatment with thiazolidinediones increases the
risk of fractures by up to 4-fold in postmenopausal women and
in men.45,46 This risk correlates with the duration of treatment
with thiazolidinediones and is significant after 12 to 18
months.47 Thiazolidinediones should be avoided in patients
with established osteoporosis or at high risk for fractures.45,46
Patients on thiazolidinediones should be assessed by dual-
energy X-ray absorptiometry and thiazolidinediones should be
Mazziotti et al Drugs and Osteoporosis
discontinued if significant bone loss occurs, although revers-
ibility of bone loss is unknown.45,46
PSYCHOTROPIC AND ANTICONVULSANT
THERAPY
Selected drugs with central nervous system effects may alter
skeletal metabolism. This has clinical relevance because
patients taking these drugs are often elderly and frail, with
a propensity to fall and, consequently, to fracture.
Selective Serotonin Reuptake Inhibitors
Selective serotonin reuptake inhibitors, agents used for the
treatment of depression, can cause bone loss. Functional
serotonin receptors and transporters are present in osteo-
blasts and osteocytes, and serotonin can influence bone
metabolism.48 Postmenopausal women on selective seroto-
nin reuptake inhibitors exhibit bone loss and a 2-fold in-
crease in the risk of nonvertebral fractures.49 There are no
specific guidelines for the prevention of the bone loss ob-
served with selective serotonin reuptake inhibitors, but
screening of women on these drugs for osteoporosis and
appropriate therapy should be considered.
Anticonvulsants
Anticonvulsants are used in epilepsy, psychiatric conditions
and in chronic pain management. Anticonvulsants may
cause bone loss, but the mechanisms are unclear. There is
accelerated vitamin D metabolism, but anticonvulsants also
may have direct inhibitory effects on osteoblast differenti-
ation, and valproate and carbamazepine have anti-andro-
genic effects.50
Low serum 25-hydroxyvitamin D levels, high bone turn-
over, and secondary hyperparathyroidism can occur in pa-
tients on anticonvulsants, decreasing BMD and increasing
the risk of fractures by 2-fold.50 BMD loss correlates with
treatment duration. Most of the fractures are nonvertebral
and tend to occur in younger individuals, suggesting that
epilepsy itself may contribute to an increased risk of osteo-
porosis and fractures. There is limited understanding of the
pathogenesis of this skeletal disorder, so diagnostic and
therapeutic guidelines have not been established. Calcium
and vitamin D supplementation is recommended. Because
anticonvulsants accelerate vitamin D metabolism, doses re-
quired to correct vitamin D deficiency may be greater than
those required in the general population.
DRUGS USED FOR CARDIOVASCULAR DISEASES
Heparin
Heparin is effective in the prevention and treatment of
venous thromboembolism. In vitro, heparin inhibits the dif-
ferentiation and function of osteoblasts.51 In vivo, heparin
decreases bone formation and increases bone resorption, the
latter by inhibiting the expression of osteoprotegerin, a
decoy receptor for receptor activator of nuclear factor–
kappa B ligand.51
881
In pregnant women, up to one third of patients placed on
heparin have a significant decrease in BMD, with fractures
occurring in only 2.2%-3.6% of all cases.52,53 In nonpreg-
nant women, the incidence of fractures is higher, and ⬃15%
of patients experience vertebral fractures 3-6 months after
starting heparin.54 Fragility fractures are less frequent in
patients on low-weight heparin than unfractionated hepa-
rin.54 Moreover, the newly developed anticoagulant
fondaparinux does not cause bone loss and may be consid-
ered as an alternative to heparin in osteoporotic patients.55
Oral Anticoagulant Therapy
Oral anticoagulants are often used in older subjects to pre-
vent or treat deep vein thrombosis; their effects on bone
metabolism are controversial. Anticoagulants are vitamin K
antagonists that interfere with gamma-carboxyglutamate
formation, and consequently inhibit the accumulation of
osteocalcin in the extracellular matrix.56 Although these are
potentially negative effects, evidence that these drugs cause
osteoporosis and fractures in the general population is
insufficient.57,58
Loop Diuretics
Loop diuretics are often used in the management of con-
gestive heart failure, which itself is associated with an
increased risk of fragility fractures.59 Loop diuretics inhibit
sodium and chloride reabsorption and consequently inhibit
calcium reabsorption, increasing its renal excretion and
bone turnover.60 This results in decreased BMD and in-
creased risk of fractures in men and postmenopausal women
on long-term treatment with these drugs.61,62 Most of the
fractures are nonvertebral.
DRUGS TARGETING THE IMMUNE SYSTEM
Calcineurin Inhibitors
Calcineurin inhibitors are immunosuppressants used in
combination with glucocorticoids in patients undergoing
organ transplantation. In vitro, cyclosporine and tacrolimus
inhibit osteoclastogenesis and bone resorption.63 However,
in vivo, these drugs cause bone loss due to markedly in-
creased bone resorption.64 Changes in T-cell cytokine pro-
duction and altered vitamin D metabolism with secondary
hyperparathyroidism may contribute to the effects of cal-
cineurin inhibitors. Furthermore, it is not possible to isolate
the contribution of the underlying disease and glucocorti-
coids from their effects on BMD and fragility fractures.65
Fracture risk is related to the patient age and the underlying
disease.65 Older age and lower BMD are predictors of
vertebral fractures in patients with cardiac disease, but not
in those with liver disease. In this condition, prevalent
vertebral fractures are the only predictors of future vertebral
fractures.66 BMD is of modest value in patients with end-
stage renal disease because of renal osteodystrophy.
Because bone loss occurs in the initial months of immu-
nosuppressive therapy, treatment should be instituted early.
882 The American Journal of Medicine, Vol 123, No 10, October 2010
Calcium and vitamin D supplementation, and antiresorptive
agents should be considered for the prevention of bone loss
occurring after transplantation with uncertain effects on
fracture risk.67
Antiretroviral Therapy
The introduction of antiretroviral therapy significantly re-
duced morbidity and mortality in patients suffering from
human immunodeficiency virus (HIV). Antiretroviral drugs
cause bone loss by increasing osteoclastogenesis and bone
resorption, and by causing mitochondrial damage, impairing
osteoblastic function and bone formation. These effects lead
to a decrease in BMD.68
Data on fracture incidence are limited, and studies on
HIV patients do not discriminate between those receiving
and not receiving antiretroviral therapy. The relative risk of
vertebral and nonvertebral fractures increases by about 40%
and 70%, in females and males with HIV infection, respec-
tively.69 Currently, antiretroviral therapy-induced bone loss
is managed with a reduction of risk factors, supplemental
calcium and vitamin D, and physical exercise. Alendronate
and zoledronic acid increase BMD in HIV patients, but their
benefit on fracture reduction is not documented.70,71
DRUGS USED FOR GASTROINTESTINAL
DISEASES
Proton Pump Inhibitors
Proton pump inhibitors are commonly used in the treatment
of diseases of the upper gastrointestinal tract. In vitro, the
inhibition of proton pumps on the osteoclast ruffled border
may decrease bone resorption.72 However, proton pump
inhibitors decrease intestinal calcium absorption, increasing
bone resorption in vivo. Proton pump inhibitors decrease
BMD at the lumbar spine and hip, and increase the risk of
vertebral and nonvertebral fragility fractures, depending on
drug dose and duration of therapy.73,74 Fracture risk is
reversed 1 year after proton pump inhibitors withdrawal.
Histamine-receptor 2 blockers do not cause bone loss.75
CONCLUSIONS
Drugs routinely used for treatment of multiple diseases have
detrimental effects on the skeleton. Awareness of this clin-
ical problem is limited, and consequently, preventive mea-
sures are often not undertaken. Adequate monitoring of
bone health and therapeutic intervention are recommended
when drugs with an adverse bone safety profile are used,
particularly in patients with additional risk factors for
osteoporosis.
ACKNOWLEDGMENT
The authors thank Mary Yurczak for secretarial assistance.
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