There progressive bone loss in Rheumatoid Arthritis (RA) has a number of causes. The
development of chronic inflammation impacts on the immune system and
this leads to signs and symptoms that may enhance bone loss. Anorexia,
malnutrition, muscle wasting, cachexia and depression are directly or
indirectly related to chronic inflammation.
capacity and lack of exercise associated with joint pain and deformities
further contribute to progressive bone loss. Most importantly, the use
of corticosteroids during RA treatment, even a small dose of prednisone
of 5mg/day or equivalent for more than three months, is associated with
rapid and persistent loss of bone.
‘Early and aggressive treatment of Rheumatoid Arthritis with biologic drugs may be most effective in halting progressive bone loss in patients with Rheumatoid Arthritis.’
A new review by the International Osteoporosis Foundation (IOF)
Chronic Inflammation and Bone Structure (CIBS) Working Group concludes
that early and aggressive treatment of Rheumatoid Arthritis with
biologic drugs, specifically biological disease-modifying anti-rheumatic
drugs (DMARDs), may be most effective in halting progressive bone loss
in patients with RA.
Co-Author Dr. Cristiano Zerbini, Director of the Centro Paulista
de Investigação Clinica (CEPIC) in Sao Paolo, Brazil, stated, "Bone loss is one of the most harmful effects induced by chronic
inflammation as well as by medications taken to treat rheumatoid
arthritis, such as glucocorticoids. It is therefore important that we
gain a better understanding of which medications used to treat patients
with chronic inflammation are less likely to impact negatively on bone
One study has shown that continuous
treatment with prednisone at 10 mg/day during 90 days or more increased
the risk of vertebral fractures 17-fold and hip fractures seven-fold.
The review 'Biologic therapies and bone loss in rheumatoid arthritis'
presents the best evidence available regarding bone loss in RA
patients. It takes an in-depth look at the mechanisms of bone
destruction in RA, including: RA serum markers and bone loss;
anti-citrullinated protein antibodies (ACPAs) and bone; effects of
biologic DMARDs on bone such as TNF inhibitors and their effects on
bone mineral density (BMD)and on biochemical markers of bone turnover;
and Interleukin-6 blockade. It also reviews the latest information on
biologic therapies that target the lymphocyte, specifically the blockade
of the B-lymphocyte; co-stimulation blockade; biologic anti-osteoclast
The Working Group concluded that:
- Early and "aggressive" treatments were more effective in
rapidly achieving a low level of inflammation and halting the
progressive loss of bone.
- Therapies targeting specific cytokines and its signaling
pathways with biologic DMARDs may protect the skeleton and should be
introduced as soon as possible. However, it should be noted that
outcomes in these clinical studies were based mostly on changes in
biological markers and only a few reported modifications on BMD or
localized osteoporosis. Only three retrospective studies reported
reduction in fracture risk after anti-TNF therapy.
- The TNF blockade studies showed that, even in RA patients not
responsive to treatment, a protective effect on bone was observed
suggesting the possibility that anti-TNF therapy may restore coupling of
the bone remodeling independently of its anti-inflammatory action.
- Lack of efficacy of TNF blockade on hand bone loss was found,
despite its preservation of BMD in lumbar spine and hip. Better results
regarding localized bone loss were observed with anti-IL6 treatment.
- Very few studies reported inhibition of bone loss after rituximab and abatacept treatment.
- Anti-RANKL therapy showed beneficial effects in the
preservation of bone mass in RA, especially in juxta-articular
osteoporosis, although this treatment cannot alter the inflammatory
- New non-biologic therapies but potent inhibitors of the
cytokine network may offer future options for skeleton preservation in
Professor Patricia Clark, Co-author, Head of Clinical Epidemiology, Hospital Infantil de Mexico, Mexico City, stated, "Although several studies reported favourable actions of biologic
therapies on bone protection, it is clear that there are still unmet
needs for research into their actions on the risk of bone fractures in
RA patients. In the meantime, we recommend that all physicians treating
RA remain vigilant of the high risk of bone loss and fractures in their
patients. For many such high risk patients, it is important that
osteoporosis treatment be considered to reduce fracture risk."