Geriatrics - July 2017

Osteoarthritis 111

Figure 8. Diagramatic representation of factors contributing to imbalance between TREATMENT APPROACHES
formation and destruction of cartilage

Proteoglycan ↓ Proteoglycan ↑
Collagen ↓ Collagen ↑
Metalloproteinases ↑
Metalloproteinase inhibitor ↓ Metalloproteinases ↓
Metalloproteinase inhibitor ↑

IL-1 Chondrocyte TGF-b

ensure that the same technician, exposure, adequately, codeine-containing medica-
position and other factors are controlled. tions and subsequently opioid analgesics
This is extremely difficult. The use of may need to be used.14
magnetic resonance imaging (MRI) may
be useful in this kind of research, but can The use of nonsteroidal anti-inflamma-
prove to be extremely expensive.12 tory drugs (NSAIDs) in the treatment of OA
remains controversial. Their use is probably
Recent research has shown a useful related to the analgesic properties of
protective effect from exercise, especially these agents. Major side effects of therapy
strengthening of the quadriceps muscle with NSAIDs include peptic ulceration,
for knee OA. Previously, exercise was hypertension and increased cardiovas-
discouraged because of the fear of cular complications. A new class of
causing OA from overuse of the joints. agents, known generally as COXIBS,
However, in the USA, as part of the provided superior safety for gastro-intes-
Framingham study, long-term studies have tinal toxicity, but have shown increased
shown no increase in the prevalence of incidence of hypertension, stroke and
OA in subjects who jog several kilometres heart attacks. These agents prevent the
regularly. Another important preventive production of prostaglandins by selec-
strategy for OA of the knee is weight tively inhibiting the COX-2 enzyme, which
reduction.13 Studies have shown that a five converts arachidonic acid. This COX
kg weight loss will lead to a 56 % reduction isomer is only active in inflammatory
in risk of knee OA if body mass index is conditions, so that these NSAIDs do not
greater than 25. There is no relationship lower physiologically produced prosta-
between obesity and OA of the hip. glandins, which serve important
homeostatic mechanisms in the kidney,
Disease-modifying drugs for OA have platelets and gastro-intestinal tract. The
been elusive and cartilage repair tends to reported increased risk of cardiovascular
be extremely slow or nonexistent. The use events is most likely due to the effects of
of dietary supplements in the form of these drugs on thromboxane. More
glucosamine sulphate is controversial. recent reviews of the literature suggest
There is little doubt about the additional that these dangers exist even with the
relief of pain provided by these supple- conventional NSAIDs.15
ments, which need to be used at an
adequate dose. The main objective of Preventive treatment is generally unsat-
treatment, nowadays, is to provide pain isfactory and the end result is usually joint
relief. This can be achieved with the use of failure. Total hip and knee arthroplasty has
simple analgesics in the majority of cases. been a major development in the rehabili-
If simple analgesics do not control pain tation of patients with OA of the knee and

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112 MUSCULOSKELETAL CONDITIONS AND PAIN

hip, respectively. The waiting list at most and most centres would encourage the
hospitals for these procedures is in excess prophylactic use of heparin to prevent this
of three years and depends on the exper- potentially fatal complication.16
tise of the orthopaedic surgeon. The
prosthesis, cost of theatre, anaesthesiolo- CONCLUSION
gist, as well as other direct costs related
to the surgery and materials result in the Due to the massive burden of OA on
cost to a patient of around R120 000 in a society, extensive research is continuing to
private hospital. At Groote Schuur develop ways to control this serious
Hospital, over 1 200 patients are currently disease associated with ageing. Much is
awaiting knee or hip joint replacement. being learnt about the biochemical
Sadly, many of these remain confined to changes accompanying OA, but the
a wheelchair due to major difficulties with impact of these on therapy are still unclear
walking. and experimental. Promising results are
being shown from animal experiments
The initial treatment is usually with simple and some of the exciting developments
analgesics, predominantly paracetamol. may be with the use of stem cells that are
The next step would be to use combined programmed to mature into cartilage-
paracetamol plus codeine. If this fails, one producing cells (chondrocytes). The use of
would need to go onto tramadol or stronger this agent in humans is likely to be some
codeine compounds. Intra-articular injec- years in the future. Until then, analgesic
tion into a single joint sometime produces therapy and eventually joint replacement
prolonged relief and may be repeated surgery remain the treatment of choice for
every three months, especially in patients all patients with progressive OA of the
having to sit through long waiting lists for knee and/or hip. In many patients, the
surgery. Eventually, the quality of life may pain may be unrelated to the OA demon-
only be improved by joint arthroplasty. strated radiologically and it may be arising
from the non-articular structures such as
WHEN TO REFER ligaments, tendons and bursae. Occa-
sionally, the pain may be referred from
Osteoarthritis is generally a condition another area such as hip disease causing
treated in the primary health-care setting. pain in the knee. In spite of the increased
The above therapeutic measures will be knowledge about OA and the extensive
effective in treating the majority of research around OA, much still remains
patients. The main indication for referral to unknown about the disease.
a rheumatology or orthopaedic unit
would be for a decision regarding surgery, REFERENCES
or if the source of the pain is not clear. The 1. Gabriel S, Crowson C, O'Fallon W. Costs of
timing of surgery is determined by the
extent of pain and disability suffered by osteoarthritis: estimates from a geographi-
the patient, rather than the extent of cally defined population. J Rheumatol.
changes observed on the x-ray. There is a 1995;22(Suppl 43):23-25.
reasonable correlation between the 2. Vos T, Murray CJL, Barber R, et al. Glo-
severity of radiological change and bal, regional, and national incidence,
extent of pain, but disability is not always prevalence, and years lived with disability
proportional to the changes seen on for 301 acute and chronic diseases and
x-ray. Trochanteric bursitis, pes anserine injuries in 188 countries, 1990-2013: a
bursitis and De Quervain's tenosynovitis systematic analysis for the Global Burden of
are not uncommon in patients with Disease Study 2013. Lancet. 2015;386
co-existing mild OA, and significant pain (9995):743-800.
relief can be achieved from local corti- 3. Ghosh P. Articular cartilage: what it is, why it
sone injections in these situations. Deep fails in osteoarthritis, and what can be done
venous thrombosis is more common about it. Arthritis Care Res 1988;1:211-221.
following lower limb surgery of this nature 4. Messier SP, Loesser RF, Mitchell MN, et al.
Exercise and weight loss in obese older adults
HANDBOOK OF GERIATRIC MEDICINE with knee osteoarthritis: a preliminary study. J
Am Geriatr Soc. 2000; 48:1062-1072.

Osteoarthritis 113

5. Dequeker J, Boonen S, Aerssens J, et al. 12. Cibere J, Sayre EC, Guermazi A, et al. Do TREATMENT APPROACHES
Inverse relationship osteoarthritis-osteopo- physical examinations predict OA progres-
rosis: What is the evidence? What are the sion based on MRI? Results from the
consequences? Br J Rheumatol. 1996; Vancouver knee osteoarthritis progression
35:813-818. study. Osteoarthritis and Cartilage.
2011;19:S148.
6. Abramson SB, Attur M. Developments in the
scientific understanding of osteoarthritis. 13. Huang MH, Chen CH, Chen TW, et al. The
Arthritis Res Ther. 2009;11:227. effects of weight reduction on the rehabili-
tation of patients with knee osteoarthritis
7. Felson DT, Anderson JJ, Naimark A, et al. and obesity. Arthritis Care Res. 2000;
Obesity and knee osteoarthritis. The 13:398-405.
Framingham Study. Ann Intern Med.
1988;109:18-24. 14. Chou R, Fanciullo GJ, Fine PG, et al. Clinical
guidelines for the use of chronic opioid
8. Bierma-Zeinstra SM, Oster JD, Bernsen RM, therapy in chronic noncancer pain. J Pain
et al. Joint space narrowing and relation- 2009;10:113-30.
ship with symptoms and signs in adults
consulting for hip pain in primary care. 15. American College of Rheumatology Ad
Journal of Rheumatology. 2002;29 Hoc Group on Use of Selective and
(8):1713-1718. Nonselective Nonsteroidal Anti-inflam-
matory Drugs. Recommendations for use of
9. Williams CJ, Jimenez SA. Heredity, genes selective and nonselective nonsteroidal
and osteoarthritis. Rheum Dis Clin North anti-inflammatory drugs: an American
Am. 1993;19:523-543. College of Rheumatology white paper.
Arthritis Rheum. 2008;59:1058-73.
10. Brighton S, et al. Management of osteo
arthritis – clinical guideleine 2000. South 16. Amin AK, Clayton RA, Patton JT, et al. Total
African Medical Journal. 2003; 93:1012- knee replacement in morbidly obese
1020. patients. Results of a prospective, matched
study. Journal of Bone and Joint Surgery –
11. Wandel S, Juni P, Tendal B, et al. Effects of British Volume. 2006;88(10):1321-1326.
glucosamine, chondroitin, or placebo in
patients with osteoarthritis of hip or knee:
network meta-analysis. BMJ. 2010; 34:c4675.

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114 MUSCULOSKELETAL CONDITIONS AND PAIN

Osteoporosis

Dr AJ de Weerd imbalance in bone turnover – either
MB ChB MMed (O&G) increased osteoclastic bone resorption,
 Specialist in Osteoporosis, Osteoporosis which can be caused by reduced
Clinic, Pretoria East Hospitral, Pretoria oestrogen levels in postmenopausal
women, or reduced osteoblasctic bone
Osteoporosis is the most common meta- formation, which can occur as a result of
bolic bone disease, affecting one in two oral glucocorticoid therapy. Bone strength
women and one in five men aged older reflects the integration of bone mass
than 50 years in the western world. Women density and bone quality.3,4 Bone quality is
have a 50 % lifetime risk at age 50 of determined by bone geometry, turnover,
having an osteoporotic fracture and a micro-architecture, modelling and
20 % risk of having a hip fracture. The one- remodelling, and material content (which
year mortality rate for hip fracture in includes mineral, collagen, crystal struc-
women is approximately 20 %. The ture and micro-damage). In patients with
average hospital stay for hip fracture is 25 osteoporosis, low-trauma fractures, also
days, 23 days for pelvic fracture. The cost known as insufficiency fractures, occur
of one hip fracture is approximately most commonly in the wrist, spine and
R120 000. The burden of cost of fractures is hip.5 Such fractures, particularly those of
estimated to be €31 billion in France, the hip, cause considerable morbidity
Spain, Sweden and the UK in 2010. and mortality with consequent individual
and societal effects.6
DEFINITION
The various parameters listed can be
The World Health Organization (WHO) determined in vivo, using
defines osteoporosis as a systemic skeletal n D ual-energy X-ray absorptiometry
disease that is characterised by low bone n CT and quantitative CT
mass and micro-architectural deteriora- n Measurement of bone turnover
tion of bone tissue, with a consequent
increase in bone fragility and susceptibility markers
to fracture which usually involves the wrist, n H igh-resolution CT and high-resolution
spine, hip, ribs, pelvis or humerus.1 In 1994
the WHO proposed a stratified definition of MRI and in vitro, using nano-imaging
osteoporosis, which was updated in 2008, technologies (e.g., synchrotron)
that encompassed the concepts of both
low bone mass and fracture. Improved reporting of radiographic
features that suggest osteoporosis and the
CAUSES presence of vertebral fracture, which are
powerful predictors of future fractures,
According to this classification, there are could increase the frequency of appro-
four general categories: normal, low bone priate DXA referrals. Quantitative CT
mass (osteopenia), osteoporosis and remains predominantly a research tool,
severe osteoporosis.² In childhood, osteo- but has advantages over DXA – allowing
porosis can occur as a consequence of measurement of volumetric density, sepa-
defective or reduced bone formation that rate measures of cortical and trabecular
results in low peak bone mass. Inherited bone density, and evaluation of bone
diseases, such as osteogenesis imperfect, shape and size. High-resolution imaging,
and acquired chronic disease that cause using both CT and MRI, has been intro-
immobilisation or malnutrition can result in duced to measure trabecular and cortical
low peak bone mass. In adults, osteopo- bone microstructure. Although these
rosis is caused by disorders that result in an methods provide detailed insights into the
effects of disease and therapies on bone,
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Osteoporosis 115

they are technically challenging and not fracture, e.g., vertebral fractures, propen- TREATMENT APPROACHES
widely available, so they are unlikely to be sity to falls, hypovitaminosis D and so on. It
used in clinical practice. furthermore ignores the dose-effect of risk
factors such as glucocorticoid use and
RISK FACTORS cannot assess young individuals. Its major
limitation for local application is the near
Dual-energy X-ray absorptiometry (DXA) is total absence of South African fracture
the most widely available and commonly data. To prevent anxiety with the diag-
used method for clinical diagnosis of nosis of osteopenia in patients at a
osteoporosis and will remain so for the relatively young age (<65), the FRAX® tool
foreseeable future. The WHO 10-year can be a significant advantage.
fracture risk assessment tool (FRAX®)7 will
improve clinical use of DXA and the cost- AN INTEGRATED APPROACH
effectiveness of therapeutic intervention. TO FRACTURE-RISK ASSESSMENT –
Employing meta-analyses from 12 large THE NOFSA MODEL 8
prospective population studies (<60 000
subjects), John Kanis and his team at the NOFSA published the following recom-
WHO have recently identified a number of mendations on an integrated approach
robust clinical risk factors (CRFs) that to manage osteoporosis in postmeno-
appear to predispose to fracture in most pausal women and men over the age of
populations. These include: 50 years.
n A n advanced age n T reatment should be considered when
n Previous fragility fracture
n Family history of osteoporotic hip a prior fragility fracture is present.
n T reatment should be considered when
fracture
n Bone-toxic drugs such as the DXA T-score is below -2.5 at the hip
or spine.
glucocorticoids n Treatment should also be considered in
n Lifestyle factors (e.g., alcohol, patients with osteopenia (T-score
between -1.0 and -2.5) after careful
smoking, physical inactivity, diet) consideration of CRFs and BMD values.
n Excessive leanness (BMI <19 kg/m²) Fracture risk is three- to fivefold lower in
n P ropensity to falls patients aged 50 years compared with
n T he secondary osteoporosis those aged 85 years. Incorporating the
major clinical risk factors, NOFSA has
Having identified the major clinical risk proposed a simple clinical algorithm
factors for the development of osteopo- for the management of osteoporosis
rosis, the WHO team proceeded to assess and the need to intervene with potent
their relative clinical importance (weight, bone-active drugs (see Figure 1).
interactions) and along with femoral BMD
compiled the FRAX® assessment model. Clinical risk factors:
The model output is the estimated 10-year n Advanced age
probability of either a hip fracture alone or n Prior fragility fracture
the major osteoporotic fractures (spine, n Family history
hip, wrist and humerus) combined. n Alcohol/smoking/diet
n Excessive leanness
The model does not signify an interven- n Fall propensity
tion threshold, but merely indicates a n Secondary osteoporosis
fracture probability. It is further suggested
that, in the absence of a model for a PHARMACOLOGICAL TREATMENT
particular country, a surrogate country
should be used, based on the likelihood Medications used to treat osteoporosis fall
that it is representative of the index country. into two classes: The antiresorptive drugs
slow the resorption of bone – an osteo-
Although a number of limitations of the clastic activity, while the anabolic drugs
FRAX® tool have been noted, i.e., models
do not include a number of risk factors for HANDBOOK OF GERIATRIC MEDICINE

116 MUSCULOSKELETAL CONDITIONS AND PAIN

Figure 1. Algorithm for the management of osteoporosis in postmenopausal women and
men aged ≥50 years

Women and men with CRFs Clinical risk factors
Prior osteoporotic fracture** • Advanced age
• Prior fragility fracture
• Family history
• Alcohol/smoking/diet

Yes* No • Excessive leanness
≤2,5 • Fall propensity

Measure BMD*** • Secondary osteoporoses

T-score Consider

<-1.0 to >-2.5 FRAX ≥-1.0

>75yr 65-75 yr <65 yr
+

≥2 CRFs

Yes No

Individualised assessment
of CRFs + BMD

Yes ? No

BTMs Reassess
in 24/12

Consider specific treament Lifestyle measures only

* Also measure BMO; ** Fracture of hip, spine, wrist, pelvis or humerus; *** Hip, spine, ± wrist

stimulate new bone formation – an osteo- DUAL ACTION
blastic activity. Strontium ranelate is a dual-action drug.

ANTIRESORPTIVES SELECTION OF DRUGS
The largest group of drugs used to slow the
resorption of bone are the bisphospho- The reality is that all drugs halve the frac-
nates and the best known are alen- ture risk and data differ depending on the
dronate, risedronate, ibandronate and design of the drug study and the fracture
zoledronic acid. Other drugs slowing risk in the population studied.
resorption are oestrogens and the selective
oestrogen receptor modulator, raloxifene. In most cases, the side effects will force
the clinician to individualise treatment.
ANABOLICS
The main drugs presently available are the The epithelium of the oesophagus is very
parathyroid hormone (PTH 1-84) or its sensitive to bisphosphonates and patients
N-terminal fragment (PTH 1-34), called with reflux disease and difficulty in swal-
teriparatide, which are given daily by lowing cannot use oral bisphosphonates.
subcutaneous injection. The drug cannot be broken into smaller
pieces.

Osteonecrosis of the jaw (ONJ) was first
published in 2004, referring mostly to use in

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