Approach to bone protection in multiple sclerosis

Patients with multiple sclerosis (MS) are at increased risk of fragility fracture as a consequence of reduced mobility, propensity to fall and low bone mass [1–3]. In this issue of the journal, Tyblova et al. publish their findings of a very large cohort with baseline and longitudinal data from a single centre. They conducted comprehensive multivariable analyses that explored associations with bone mineral density (BMD) and with fracture. They found that disability, not steroids, had the strongest association with both BMD and fracture [4]. This finding concurs with a previous population-based study from Denmark [5]. The questions that arise for patients with MS are the following: Who should be screened? What are the indications for treatment? What treatment should be given and for how long? When should patients be rescreened? Answers to these questions are to be found, in part, in the bone literature. Conceptually, osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture [6]. Clinically, osteoporosis can be defined by the history of fragility fracture that is caused by a low trauma, namely from the force of a fall from a standing height or less – most commonly vertebral, hip and wrist. It is worth noting that there are no symptoms until fracture occurs. Operationally, osteoporosis is diagnosed prior to fragility fracture by measuring BMD at lumbar spine and hip using dual-energy X-ray absorptiometry (DXA). The WHO classification criterion for osteoporosis is based on the T score, which compares an individual’s BMD with the mean value for young normals and expresses the difference as a standard deviation score. Osteoporosis is a T score at or below 2.5. Low bone mass (osteopenia) is a T score between 1.0 and 2.5 [6]. The most widely applied fracture risk prediction model is FRAX [6]. For those aged 40–90 years, it uses the DXA result from the femur neck and clinical risk factors (age, sex, prior fragility fracture, parental history of hip fracture, current tobacco smoking, ever long-term use of glucocorticoids, rheumatoid arthritis or other secondary causes, and alcohol intake three or more units daily). It has been argued that MS should be considered as an independent risk factor for osteoporosis [7]. FRAX estimates the 10-year risk for major fractures (hip, vertebra, wrist and humerus) and for hip fracture alone. This can and should be calculated at the time of DXA, with all densitometers having updated software. For MS patients, FRAX has a major limitation in that it does not have a metric for falls. The National Osteoporosis Foundation (NOF) recommends that individuals should be considered for bone protection under the following circumstances: (i) a fragility fracture at hip or spine; (ii) a T score of ≤ 2.5 at spine, femur neck or total hip site; or (iii) a FRAX score of ≥20% for major fracture or of ≥3% for hip fracture [6]. The anti-fracture efficacy has been established for a number of agents: bisphosphonates (oral and intravenous), parathyroid hormone (PTH134) and a RANK-ligand inhibitor (denosumab); and to a lesser extent for selective estrogen receptor modulators [6]. The BMD response to bisphosphonates tends to plateau at about 5 years. Prolonged bisphosphonate therapy is associated with atypical femoral fracture; a ‘drug holiday’ is often advocated. A daily subcutaneous injection of PTH1-34 for 2 years is particularly effective in increasing BMD at the spine. Denosumab is like bisphosphonates in that it suppresses bone remodelling but with a much shorter offset effect; extension studies indicate that BMD continues to increase over time without a plateau effect. For bone health, NOF advocate a total daily calcium intake of 1000 mg and a total daily vitamin D intake of 800 IU (20 lg) [6]. More research on pharmacological and non-pharmacological intervention is needed to establish guidelines for maintenance of bone health in MS. Hearn and Silber recommended DXA scanning in all the following cases: postmenopausal women; Extended Disability Symptom Scale (EDSS) score ≥6.0; prior fragility fracture; prolonged glucocorticoid treatment; and current epilepsy medication [8]. Although the results presented by Tyblova et al. [4] support this view, the high prevalence of osteopenia during the early stages of the disease argue for a more active approach. We suggest that BMD assessment by DXA should be performed for all MS patients over 40 years