Download How common medicines can affect bone health

Nursing Practice
Review
Medicines management
Keywords: Drug-induced osteoporosis/
Fracture/Bone health/Bone protection
●This
article has been double-blind
peer reviewed
Drugs used to treat common conditions can adversely affect bone health.
Nurses need to be aware of the risks and prevention strategies
How common medicines
can affect bone health
eview of common drugs that adversely affect bone health
R
Mechanisms that have a negative effect on bone density
Overview of prevention strategies
Author Sharon Rees is reader in
pharmacotherapeutics at London South
Bank University.
Abstract Rees S (2014) How common
medicines can affect bone health. Nursing
Times; 110: 32/33, 25-27.
Many people have weak bones and this is
a global public health concern. Lifestyle
factors can reduce bone density, as can
some common drugs. This article
describes some of these drugs, the
conditions for which they may be
prescribed and how they can threaten
bone health. Strategies to reduce the risk
of fracture and weak bones are outlined.
W
eak bones are a major
public health problem,
with associated fractures
affecting one in three
women and one in five men aged over
50-years-old worldwide (Ström et al, 2011).
Many factors threaten bone health, particularly in ageing populations. Lifestyle
factors including diet, exercise, smoking
and alcohol intake, morbidities such as
cancer and endocrine disease, genetics and
some common drug groups such as corticosteroids all contribute to low bone mass.
A continually renewing and adaptable
tissue, bone is controlled by factors that
alter the balance between bone-building
cells (osteoblasts) and bone-resorbing cells
(osteoclasts). Osteocytes, which are
embedded in the bone matrix, regulate
bone mass, receiving signals from hormones, local mediators and growth factors.
If an imbalance between bone breakdown and bone production arises, for
example from a drop in oestrogen levels
during the menopause, bone can lose mass
and become brittle. Such changes are
identified as a loss of bone mineral density
on a dual-energy X-ray absorptiometry
(DEXA) scan, with osteoporosis defined as
a bone mineral density <2.5 standard deviations below the average for young, healthy
adults (World Health Organization, 1994).
This makes fracture more likely in events
not usually associated with fracture such
as a minor injury; this is sometimes called
a low-energy/trauma fracture.
This article focuses on drugs that harm
bone density; some common ones are set
out in Table 1. The British National Formulary (British Medical Association and Royal
Pharmaceutical Society, 2014) shows this in
various ways, sometimes listing osteoporosis as a side-effect – for example, for corticosteroids and methotrexate – or describing
an “increased risk of fracture” for example,
with proton pump inhibitors (PPIs). If the
BNF or the Summary of Product Characteristics (Electronic Medicines Compendium,
2013) do not mention bone mass loss as a
side-effect, it should be taken to mean that
there is insufficient evidence of an effect.
Corticosteroids
The systemic effects of corticosteroids,
such as oral prednisolone, are the most
common cause of secondary osteoporosis
(osteoporosis resulting from another illness/condition) (Mazziotti et al, 2006). The
systemic effects on bones have two phases,
which are characterised as follows:
» Phase one – rapid bone loss from
reduced calcium absorption from the
gut and increased parathyroid hormone activity (enhanced osteoclastic
activity raises serum calcium levels);
» Phase two – decreased bone formation
and turnover, further compromising
bone structure (Pennisi et al, 2006).
5 key
points
1
Weak bones are
a major public
health issue;
related fractures
affect one in three
women and one in
five men aged >50
years worldwide
Lifestyle
factors
including diet,
exercise, smoking
and alcohol intake
affect bone health
Common drug
groups such as
corticosteroids,
proton pump
inhibitors and
heparins contribute
to low bone mass
Nutritional
advice, weightbearing and
strength-building
exercise, stopping
smoking and
limiting alcohol
intake can improve
bone health
Prophylactic
intervention is
recommended with
some drugs, such
as corticosteroids,
to reduce the risk
of osteoporosis
2
3
4
5
Osteocyte: these cells act on chemical
signals that influence bone mass
www.nursingtimes.net / Vol 110 No 32/33 / Nursing Times 06.08.14 25
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In this article...
Nursing Practice
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Table 1. Common drugs that affect bone density
Drug/drug group
Risk
BNF (BMA and RPS, 2014)
SPC (2013)
Risk level
(BNF or SPC)
Corticosteroids
● Osteoporosis, particularly in
older people
● Greatest risk in women after menopause
Not stated
Pioglitazone
Treatment for type 2
diabetes
● Increased risk of fractures in
women and older people
● Fractured bone
Common (SPC)
Proton pump inhibitors
● Increased risk of fractures,
particularly when used at high
doses for >1 year in older people
● Fracture of hip, wrist or spine
Uncommon (SPC)
Carbamazepine
Anti-epileptic
● Osteoporosis
● Not mentioned
Very rare (BNF)
Medroxyprogesterone
acetate
Hormonal contraceptive
● Reduction in BMD
● Osteoporosis (rare)
● Osteoporotic fractures (rare)
● Osteoporosis, including osteoporotic
fractures, BMD loss (frequency unknown)
Rare (BNF)
Unknown (SPC)
Cyproterone acetate
Anti-androgen
● Osteoporosis
● Osteoporosis
Rare (BNF)
Triptorelin
Gonadotrophins
hormones (GnRH)
agonists
● Osteoporosis
● Use of gonadotrophin hormones (GnRH)
agonists may cause a reduction in bone
mineral density
● Osteoporosis, no data
Not stated
Unfractionated heparin
● Osteoporosis
● Prolonged dosing may cause osteoporosis.
Significant bone demineralisation has been
reported in women on >10,000IU heparin per
day for ≥6 months
Not stated
Low-molecular-weight
heparins
● Osteoporosis (risk lower with
low-molecular-weight heparins
than unfractionated heparin)
Rare (SPC)*.
For drugs used in children, the effects are the same unless otherwise stated.
Risk-level key: very common ≥10%; common ≥1% and <10%; uncommon >0.1% and <1%; rare < 0.1%; very rare <0.0001%; unknown
(cannot be estimated from the available data)
BMD = bone mineral density. GnRH = gonadotropin-releasing hormone.
BNF = British National Formulary. SPC = summary of product characteristics
Source: British Medical Association and Royal Pharmaceutical Society (2014); Electronic Medicines Compendium (2013)
Hormone therapy
As part of their role, oestrogens, androgens
and corticosteroids regulate the production and lifespan of bone cells; it follows
that hormone therapy could damage bone.
Contraceptive drugs such as medroxyprogesterone acetate (Depo-Provera injection) are anti-oestrogenic and are associated with a reduction in bone mineral
density in the first two to three years of
use, which then stabilises (BMA and RPS,
2014). The lower oral doses of medroxyprogesterone acetate used to treat endometriosis are not associated with this rare effect
(Table 1). One reason for this difference
may be that reduced bone density arises
from the drug’s stimulation of corticosteroid receptors and not from decreased
oestrogen levels, an effect seen only at
higher doses (Ishida et al, 2008).
Gonadotrophin hormones regulate
normal growth, sexual development and
reproductive function. Drugs that reduce
gonadotrophin release, such as triptorelin,
are used to treat breast and prostate cancer,
endometriosis and infertility. These drugs
reduce oestrogen and androgen production and this is associated with loss of bone
mass, although the literature does not contain clinical data on osteoporosis and fracture. Some forms of breast cancer require
oestrogen-lowering drugs, such as letrozole, which is associated with osteoporosis,
and fractures are common side-effects
(McCaig et al, 2010; Folkestad et al, 2009).
Anti-androgen drugs such as cyproterone acetate, used to treat hypersexuality
and prostate cancer, can cause osteoporosis.
Proton pump inhibitors
Two mechanisms are proposed regarding
how PPIs increase fracture risk (Lau et al,
26 Nursing Times 06.08.14 / Vol 110 No 32/33 / www.nursingtimes.net
2012; Roux et al, 2009). Decreased gastricacid production could discourage the
absorption of calcium salts but, although
drugs such as cimetidine reduce gut acid,
they do not have this effect (Yu et al, 2008).
The current focus is on the effect that
PPIs have on osteoclast cells. An inhibiting
effect on osteoclasts could reduce bone
breakdown; this could improve bone mass
as osteoblasts continue to build bone but,
as bone turnover is prevented, bone quality
may deteriorate (Costa-Rodrigues et al,
2013). Investigations into the effect of PPIs
on bone health have been carried out
mainly in people aged over 70 years who
are at risk of osteoporosis (Eom et al, 2011;
Roux et al, 2009), but some studies have
shown an impact on bone in other populations, such as post-menopausal female
smokers who have been using PPIs for
more than two years (Khalili et al, 2012).
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Table 2. Guidelines for bone protection
Drug
Guideline (where available, source stated)
Corticosteroids
● Doses of >7.5mg prednisolone or equivalent per day >3 months
for any age, assess and consider prophylaxis with bisphosphonate
(>65 most at risk) (Clinical Knowledge Summaries, 2013)
● No drug protection information stated for children (BNF for
Children) (BMA and RPS, 2013)
Pioglitazone
● Assess for fracture risk before starting (CKS, 2013)
Letrozole
● Assess susceptibility to osteoporosis (bone mineral density) before
treatment and at regular intervals (BMA and RPS, 2014)
Filgrastim
● Monitor bone density if given for >6 months (BMA and RPS, 2014)
PPIs are sometimes used to offset the
gastrointestinal side-effects of bisphosphonate drugs used to treat osteoporosis.
Using PPIs in this instance may make bisphosphonates less effective (Abrahamsen
et al, 2011). National Institute for Health and
Care Excellence guidelines recommend
caution is exercised when prescribing PPIs
and bisphosphonates together (NICE, 2008).
Anti-epileptic drugs
Fractures in people taking anti-epileptic
drugs are reported for phenytoin, carbamazepine and primidone (Ali et al, 2004;
Ensrud et al, 2004) but the BNF states fracture as a risk for carbamazepine only.
These drugs are thought to accelerate the
metabolism of vitamin D, which lowers
the availability of calcium for bone formation (Ali et al, 2004; Ensrud et al, 2004).
Other biochemical abnormalities found
in patients taking anti-epileptic drugs that
may affect bone health include:
» Hypocalcaemia;
» Hypophosphataemia (low phosphate);
» Hyperparathyroidism (Pack, 2008).
Drugs for diabetes
Pioglitazone is used to treat people with
type 2 diabetes who are resistant to insulin;
it works by improving the sensitivity of
muscle and fat cells (adipocytes) to insulin.
However, the stem cells that make fat cells
and bone-building cells share the same
precursor. Pioglitazone increases the production of the more insulin-responsive fat
cells and, as a consequence, fewer bonebuilding cells are produced, leading to
osteoporotic changes (Rzonca et al, 2004).
Heparin
Long-term use of heparin is associated with
bone density loss (Bhandari et al, 1998).
High-dose whole heparin (unfractionated) inhibits bone-building cells while
encouraging activity in bone-absorbing
cells (Hansen and Vondracek, 2004). The
osteoporotic risk is lower with
low-molecular-weight heparins as the
smaller fragments have less binding
capacity to bone cells (Hirsh et al, 2008).
Managing risk
The following lifestyle factors can all help
to improve bone health:
» Sound nutritional advice;
» Engaging in weight-bearing and
strength-building exercise;
» Stopping smoking;
» Limiting alcohol intake (NICE, 2013).
There are some drugs – for example corticosteroids – for which prophylactic
intervention using a bisphosphonate drug
(which slows down bone resorption) is recommended to reduce osteoporosis risk.
However, as Table 2 shows, in most cases
there is no guide to risk reduction. When
the risk of fracture is common, for example
with pioglitazone, counselling may be
appropriate as well as monitoring through
clinical reviews and DEXA scans.
Conclusion
Drugs that are commonly prescribed can
have a detrimental effect on bone health
and their risks and benefits must be considered and discussed with patients. Nurses
need to consider the implications of the
side-effects of drugs and have knowledge
so they can discuss these with patients. NT
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