Abstract

     Osteoporosis is underrecognized and undertreated in men, even though up to 25% of fractures in patients over the age of 50 years occur in men. Men develop osteoporosis with normal aging and accumulation of comorbidities that cause bone loss. Secondary causes of bone loss may be found in up to 60% of men with osteoporosis. Mortality in men who experience major fragility fracture is greater than in women. Diagnosis of osteoporosis in men is similar to women, based on low-trauma or fragility fractures, and/or bone mineral density dual-energy X-ray absorptiometry (DXA) T-scores at or below −2.5. Because most clinical trials with osteoporosis drugs in men were based on bone density endpoints, not fracture reduction, the antifracture efficacy of approved treatments in men is not as well documented as that in women. Men at a high risk of fracture should be offered treatment to reduce future fractures.

Introduction

     Osteoporosis is a worldwide disease that causes more than nine million fragility fractures annually, one every 3 s [1].

     Men have a lower risk of osteoporosis and fragility fractures than women. This is because women have bones with smaller diameters, lower peak bone mass, a menopause-related bone resorption process, and a higher risk of falls than men [2]. Despite osteoporosis and fragility fractures being less common in men than women, 39% of osteoporotic fractures worldwide occur in men [1]. Data from 2005 indicate that of the 2 million osteoporotic fractures that occur annually in the US, 29% occur in men. This percentage corresponds to an associated cost of 17 billion US dollars [3]. In men and women, the incidence of hip fractures increases exponentially with age, although in men, the increase begins approximately 10 years later [4]. Data from the U.S. 2008 Nationwide Emergency Department Sample showed the incidence of hip fracture in men ranging from 0.56 per 1000 per year at the age of 60 years to 13 per 1000 per year at age 85 years [5]. Similar results were reported in a Norwegian study covering the years 2004–2005, with an incidence of 0.49 per 1000 person-years of hip fractures in men at age 60 and 12.3 per 1000 person-years at age 85 [6]. A 60-year-old man has an approximately 25% risk of having an osteoporotic fracture during his remaining lifetime [7]. Men are less likely than women to be evaluated and receive antiresorptive treatment after a hip fracture [8,9]. The mortality rate associated with hip fractures [10,11] and vertebral and other fractures [12] is higher in men than in women. In a prospective study in community dwelling women and men aged 60 years and older in Australia, mortality after a low trauma fracture was 48% in women and 57% in men within 10 years [13]. The reason for this difference in mortality is not clear, but higher risk of infection in men than in women after a low trauma fracture could be one explanation [14].

Conclusion

     Male osteoporosis occurs less frequently than osteoporosis in postmenopausal women but is still responsible for a substantial disease burden in the population. Approximately 25% of fractures in patients over 50 years occur in men. Osteoporosis in men increases with age as in women, and mortality after major fragility fractures is greater in men than women. Male osteoporosis is defined by the occurrence of fragility fractures, in some parts of the world, only hip and spine fractures or by DXA BMD T-scores of −2.5 or lower at the hip, lumbar spine, and/or forearm. Men having T-scores of −2.5 or lower and prior fragility fractures are at high risk of future fractures. Men with T-scores between −1.0 and −2.5 should be assessed by FRAX or similar tools to determine fracture risk. At least half of men with osteoporosis have secondary causes of bone loss, and identification and treatment of these causes may help prevent further bone loss and possibly improve bone density. Treatment trials of osteoporosis in men have led to the approval of multiple medications for use in men, although these trials were typically small, short in duration, and used bone density rather than fracture endpoints.

Abstract

     In this chapter, we emphasize among rheumatoid arthritis (RA) patients, whom and how to screen for osteoporosis. We highlight certain modalities, advancements in technology, secondary osteoporosis workup, and laboratory testing as well as their caveats. Finally, we discuss current guidance on how to direct the laboratory and radiology testing in the context of the individual patient with RA to guide and select from the osteoporosis treatment options currently available.

Introduction

     Rheumatoid arthritis (RA) is associated with double the risk of fracture when compared to the general population [1]. Unfortunately, osteoporosis screening and treatment rates are low in RA and may be due to the lack of clear guidelines for this high-risk population [2]. In this review, we collate the existing evidence to provide an evidence-based guide to osteoporosis screening and treatment for people with RA.

     There are no RA-specific guidelines for osteoporosis screening which likely contributes to the low rates of osteoporosis screening and detection in this high-risk population [2]. To provide evidencebased screening recommendations for people with RA, we combine recommendations from the 2014 National Osteoporosis Foundation (NOF) [3] and the 2017 American College of Rheumatology (ACR) glucocorticoid-induced osteoporosis (GIOP) guidelines [4]. The 2014 NOF guideline states that adults with a diagnosis (such as RA) or taking a medication (such as glucocorticoids (GCs)) should be screened. This recommendation does not apply to healthy young males or premenopausal females without fracture history. There is an additional statement to screen post-menopausal females and males over 50 with clinical risk factors for fracture. We use this statement to base our recommendation to screen all people with RA aged 50 and above [3]. The 2017 ACR GIOP guideline recommends bone mineral density (BMD) screening for anyone 40 years and older who are taking
2.5 mg prednisone equivalents per day for 3 months or longer [4]. It also provides guidance for BMD testing for people under 40 years of age with significant risk factors such as prior fracture or exposure to very high doses of GCs [4].

Conclusions

     Early case detection and screening in RA patients is critical, especially in those with high ACPA positivity, prolonged RA disease duration, significant GC exposure, or history of low trauma fracture. While there is a need for more RA-specific studies and RA-focused bone health guidelines, we advocate for the clinician to risk stratify based on existing guidelines to aid in shared decision-making with patients and choosing the appropriate osteoporosis agent for fracture prevention.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with multiple phenotypic presentations, driven by the interplay of autoimmunity and vasculopathy with excessive dermal and internal organ fibrosis. Microvascular damage is a hallmark in the pathogenesis of SSc, most often manifested clinically by Raynaud’s phenomenon, skin ulcers, and pulmonary arterial hypertension (PAH) [1, 2]. Skin ulcers represent a major challenge in SSc, affecting up to 58% of SSc patients and may involve multiple fingers and both hands. Skin ulcers are painful and have a major impact on SSc-related hand disability. SSc patients with digital ulcers (DU) have limited wrist and hand mobility, increased global and hand disabilities, and decreased health-related quality of life compared to those without active DU [3]. Ultrasound (US) is a non-invasive, low-cost, reliable method that has been increasingly used for measuring joint inflammation and damage in rheumatology [4]. It is promising in evaluation of joints and tendons in SSc patients [5]. Additionally, US has been reported to support the assessment of skin thickness in SSc patients [6]. However, there are no previous reports using ultrasonography to evaluate skin ulcers in SSc patients. Clinical assessment of skin ulcers by visual examination is commonly associated with limited ability to assess the depth of the ulcer, the degree of tissue loss, the presence or absence of underlying calcinosis, and whether the ulcer is infected or not. Skin ulcer is defined histologically as a break in the epithelial integrity of the skin which may extend to deeper structures [7]. Recently, a preliminary clinical definition of skin ulcer in SSc has been developed [8]. US scanning of skin ulcers may provide a unique opportunity to better define and assess skin ulcers. To date, there has been no sonographic characterization of SSc-related skin ulcers. The availability of an objective US image of skin ulcers in SSc may have utility in clinical trials to objectively assess ulcer morphology, extent, severity, and response to treatment. It may also be useful to define and measure skin ulcers in the clinical setting. The purpose of our study was to preliminarily evaluate the ability of ultrasound (both gray scale (GS) and power Doppler (PD)) to define the morphology and extent of cutaneous ulcers in SSc patients.

Plain radiography has in the past been the primary imaging tool for investigating arthropathies. Radiographic features of the various types of arthritis have been extensively described in the literature and previously in this journal. However, structural bony changes, such as sclerosis and erosions, seen on radiographs, occur late in the course of disease, and early changes are not apparent. The sensitivity of plain films is low, and disease activity cannot be adequately assessed. Pelvic and lumbar spine radiography incurs a relatively high dose of ionizing radiation; for example, the dose from an anteroposterior radiograph of the pelvis is 35 times that from a chest X-ray. It should therefore be avoided where possible, particularly in children and adolescents. Magnetic resonance imaging (MRI) and ultrasonography are being increasingly used to aid early diagnosis of arthropathies, and this facilitates early treatment that may prevent progression to irreversible structural damage. Here we describe recent advances in the imaging of rheumatological diseases. For a more in-depth review of the role of ultrasound, the interested reader is referred to the dedicated ultrasound chapter (10.1016/j.mpmed.2017.12.010) in this publication.

Magnetic resonance imaging

MRI has emerged as the most sensitive imaging modality for detecting arthritis and discriminating between acute and chronic inflammation. In recent years, substantial technical advances have been made in software and hardware, such as phased-array coils, higher performance gradients, parallel imaging and advanced post-processing techniques. This has led to reduced scan times and improved image quality. Other advances include isotropic three-dimensional (3D) imaging techniques, which reduce partial volume artefacts and allow reformatting in multiple planes for improved visualization of anatomy and pathology. High-field strength systems (e.g. 3T MRI) are increasingly used in clinical practice, providing better spatial resolution and signal-to-noise ratio.