Consensus statement: osteoporosis prevention and treatment in Latin America—current structure and future directions

To address the above issues, the AHF identified a six-member panel of clinicians and scientists from Latin America with expertise in the field of osteoporosis and representing the disciplines of rheumatology and gynecology. Both AHF and the expert panel independently used PubMed, Embase, Lilacs (Latin American and Caribbean Literature on Health Sciences), and Scielo (Scientific Electronic Library Online) to conduct a careful review of the literature. Useful publications were identified using terms related to osteoporosis, osteopenia, osteoporosis diagnosis, osteoporosis epidemiology, and, in PubMed, combining them with country names or regional names related to Latin American and the Caribbean Islands.

The search strategy for databases was (osteoporosis diagnosis) AND ((Latin America OR Central America OR South America OR Caribbean OR Argentina OR Bolivia OR Brazil OR Chile OR Colombia OR Costa Rica OR Cuba OR Dominican Republic OR Ecuador OR El Salvador OR Guatemala OR Haiti OR Honduras OR Mexico OR Nicaragua OR Panama OR Paraguay OR Peru OR Uruguay OR Venezuela))). A total of 1039 articles were identified through the online search: 842 in PubMed, 82 in Lilacs, and 115 in Scielo. Some of them were excluded as duplicates and most were excluded after screening title. The literature review was not directed toward identifying papers related to specific treatments, but rather focused on papers that reviewed or summarized activities related to osteoporosis in Latin America. In total, 48 relevant publications were shared among the entire panel prior to their in-person meeting.

To better focus the discussion, AHF staff developed a set of generic questions related to the topic, and distributed them to the panel members before the meeting. Panel members independently drafted a response to the questions, which served as the starting point for discussion at the meeting. During the course of a multi-day meeting, the panel reviewed and discussed the published literature, and from numerous drafts and rounds of discussion, a manuscript was created based on unanimous consensus. Subsequent to the meeting, the panel reviewed the document, minor edits were made, and the panel acknowledged that they were in full agreement.

Most reports on the epidemiology of osteoporosis in LA come from 14 countries whose National Societies have membership to the International Osteoporosis Foundation. Additional studies gathered by the literature search or local publications are included as well. The reasons for a lack of data from other countries are likely to be the absence of national databases and robust surveillance methodology, reporting issues, and geographical and cultural barriers. What data is available can be grouped into the epidemiology of hip, vertebral, and other fractures.

The epidemiology in the region was summarized in the Latin America Regional Audit in 2012 [9]. Hip fracture rates in women age 50 and older ranged from 53 to 443 per 100,000 persons, and from 27 to 135 per 100,000 for men age 50 years and older, with a ratio of 2 to 3 women per man [9]. The lifetime risk of hip fracture after 50 years of age in Mexico was 8.5% in women and 3.8% in men. In Venezuela, the risk was 5.5% for women and 1.5% for men [10].

The projections of hip fractures in the region show that there will be a significant increase by the year 2050. It is estimated that in Mexico the annual number of hip fractures will increase from 29,732 in 2005 to 155,874 in 2050 [11]. In Argentina there are approximately 34,000 annual hip fractures among people over 50 years of age, with an average of 90 fractures per day [12]. It is estimated that the number of hip fractures per year in this population will almost triple by 2050. In Brazil, there are approximately 121,700 hip fractures per year, which are projected to increase to 160,000 annual fractures by 2050 [13, 14].

In Latin America the direct costs for hip fracture care vary from $3100 USD in Uruguay to $12,000 USD in Brazil [9]. In a study from Mexico, it was reported that in 2006, a little more than 97 million dollars was spent for hospital care for hip fractures. This expense was equivalent to the cost of insulin for the entire country’s insulin-dependent population for the same year [13, 15]. Another study in Mexico found that the annual cost of non-pharmacological management of osteopenia and osteoporosis, in addition to the medical care of the four main fragility fractures (hip, spine, forearm, and humerus) caused by osteopenia and osteoporosis, was 480 million of dollars in 2010. The projections for 2020 indicated that these costs will increase by 42% [16].

Vertebral fractures are the most common single osteoporotic fractures worldwide, and occur in 30–50% of people over age of 50 [17]. However, in contrast to hip fractures, 2/3 to 3/4 of these are clinically silent and less than 10% require hospital admission [18]. Moreover, even when there is a vertebral fracture on X-ray, it is often not recorded by the radiologist, rarely noted by the clinician, and consequently no treatment is provided.

Asymptomatic vertebral fractures are associated with decreased quality of life, regardless of age, body mass index, and physical activity, highlighting the importance of preventing these fractures [19]. The incidence rates of these fractures rise exponentially with age.

In 2009, the first multicenter study of radiographically identified vertebral fractures in the region was reported in a random sample of populations from Argentina, Brazil, Colombia, Puerto Rico, Mexico, and Venezuela. The study consisted of women over the age of 50 [13]. The data confirmed an exponential increase in fragility with age. The highest overall rate was in Mexico (19%) and the lowest in Puerto Rico (12%). Another study conducted in Brazil with 943 subjects older than 65 years (São Paulo Aging & Heath Study) found an overall prevalence of vertebral fractures of 29% (95% CI 26–32), with no difference between men and women [20].

Information related to other fragility fractures is scarce and comes primarily from Brazil and Mexico. The Brazilian study on osteoporosis (ARMS) [14], completed in 2009, showed that the prevalence rate of low-impact fractures ranged between 11 and 22% in men, and between 11 and 17% in women. In the Brazilian São Paulo Aging & Heath Study [21], the main fractures were distal forearm (6%), humerus (2%), and ribs (1%). In this study, a significantly higher prevalence was observed in women (17%) than in men (7%). Mexico has reported that nationwide, distal forearm fractures are the highest reported followed by hip and humerus fractures [22].

A fracture at any location results in an increased risk of subsequent fractures, with the highest risk following hip and vertebral fractures in men and women [23]. The subsequent fracture risk is not constant over time; patients are at highest risk immediately after the initial fracture is incurred, particularly in the first year. Data suggest that clinical vertebral and non-vertebral fractures cluster in time from menopause onwards. Up to 23% of the subsequent fractures occur within 1 year after the first fracture, and about 54% occur within 5 years [24]. The risk of fracture decreases with time, but does not return to baseline values [25]. In spite of the high rate of refractures, treatment with anti-resorptive drugs following a fracture is very low, ranging from 5 to 44% of eligible patients [26].

The majority of patients with any fragility fracture are not treated to prevent another fracture, even when effective treatments are available. A recent prospective observational study of > 60,000 women aged ≥ 55 years, recruited from 723 primary physician practices in 10 countries, reported that less than 20% of women with new fractures received an osteoporosis diagnosis and treatment [27]. There is a paucity of data about this situation among LA countries, but, at least in the Brazilian experience, the majority of patients with fractures due to fragility are neither evaluated nor treated for osteoporosis or for the prevention of subsequent falls [28].

The World Health Organization first convened a group of experts in 1994 to assess fracture risk and its application to screening for post-menopausal osteoporosis. Osteoporosis was defined based on bone mineral density. A standardized score, called T-score, was used to define the categories for diagnosis, which are as follows:

A dual X-ray absorptiometry (DXA) assessment will determine bone mineral density. The assessment by DXA is the gold standard for the diagnosis of osteoporosis and is an important component of assessing fracture risk. However, given the high specificity but low sensitivity of using bone mineral density for risk prediction, the combination of DXA and clinical risk factors, such as FRAX, significantly improves the sensitivity of risk prediction [29]. Moreover, the use of FRAX thresholds can reduce the need for DXA in patients identified as having either a high or low risk of osteoporotic fracture, and in some cases, patients at high risk may be considered for treatment even without BMD testing [30]. DXA is recommended for women aged 65 and older, in post-menopausal women less than 65 with risk factors, or in men age 70 and older and in younger men if they have risk factors for low bone mass [31].

One valuable tool to assess fracture risk and assist in treatment decisions is a risk calculator. The osteoporosis field has developed validated fracture risk calculators [30] that also delineate intervention thresholds for osteoporosis drug therapy. In this paper we focus on the FRAX risk calculator because of its widespread availability and use.

FRAX uses several osteoporosis risk factors and provides a 10-year probability of hip fracture and a 10-year probability of a major osteoporotic fracture (i.e., clinical vertebral fracture, spine, wrist, hip, or shoulder fracture). The FRAX index has been validated in several LA countries (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, and Venezuela), and more recently, FRAX-based therapeutic thresholds were published [32]. A FRAX assessment should be made in all men over 50 and in all post-menopausal women with a clinical risk factor or a BMI < 19 kg/m² [30]. In older populations (i.e., women over 65 and men over 75), age itself is a strong enough risk factor to warrant risk assessment. Different countries have different thresholds for recommended treatment according to FRAX values.

It is important to identify those patients who need screening, diagnosis, and treatment as soon as possible. In LA countries, a FRAX-based intervention threshold identifies those who may warrant treatment. The heterogeneity of the intervention threshold between LA countries indicates that country-specific FRAX models are more appropriate than would be a single FRAX model [32].

The advantage of FRAX compared to DXA is that the former is easily available, inexpensive, the test can be performed in a wide variety of locations, and requires less health professional training to administer. It is an ideal method of screening in primary care. It is also particularly useful in borderline cases of osteopenia, in which a patient may have a high FRAX risk, but does not yet have a T-score below − 2.5 [32].

Treatment should begin if there is a previous fragility fracture or if the T-score (i.e., DXA) is below or equal to − 2.5 at lumbar spine, total hip or femoral neck, or who are osteopenic and have a FRAX score above the designated interventional level. The drugs available either decrease bone resorption (anti-resorptives) or are anabolic agents (stimulate bone formation). Anti-resorptive therapies include bisphosphonates, denosumab, hormone replacement therapy, and selective estrogen receptor modulators (SERMs). The only bone forming therapy currently available in Latin America is teriparatide.

In addition to pharmacologic therapy, all patients should receive lifestyle modification recommendations (e.g., recommendations for physical activity, smoking cessation, nutrition counseling, and alcohol intake of < 3 units per day) and adequate calcium consumption by diet or supplements, and appropriate vitamin D supplements. Region-wide guidelines for diagnosis and treatment of osteoporosis have not been established; however, many countries have their own guidelines that specify treatments as first- or second-line options and the duration of treatment, among other relevant to that country.

Compliance with therapy is a complex process that is influenced by multiple factors. A lack of adherence to therapies is an issue for most chronic diseases, including osteoporosis. In the real world, adherence to treatment is much less than in controlled clinical trials. A lack of adherence to osteoporosis treatment will ultimately have an effect on the degree of fracture protection achieved [33]. There appear to be no studies in LA that evaluate adherence to therapy.

Since 1990, every country in the region has gone through a series of health sector reforms with the aim of increasing equity, effectiveness, and coverage. Unfortunately, despite some positive results, these reforms have not achieved their anticipated goals. The mixed composition of health systems, social and health determinants, and varying economic conditions are important issues related to access to quality health care in the region. While some health care systems provide DXA and access to certain types of drugs, others do not. As a result, there is no universal access to prevention interventions or treatment options across the region.

LA health systems are highly fragmented [34] and there is a lack of coordination between systems in a country [35]. Another important factor in LA is that approximately 21% of the population does not seek care because of geographical barriers [9].

Although pharmacologic agents to prevent and treat osteoporosis are widely available in LA, some unique disparities exist. In most countries there is at least a public health care system and a self-funded private insurance system. Both systems provide widely available, inexpensive, and effective agents (e.g., bisphosphonates), but other drugs (e.g., denosumab, teriparatide) are sometimes only available through the private insurance system. Thus, low-income patients often cannot attain access to medications that may be medically indicated.

All told, osteoporosis is not a priority for public health in most LA countries, where basic health problems such as infant mortality, vaccination, and other health problems consume most of the national budget for health. Other chronic diseases with high costs, such as cancer and diabetes, also account for a high percentage of the budget. Given the enormous toll that osteoporosis imparts on populations, and the relatively low cost of effective treatments, it is clear that much more needs to be done to elevate the commitment by the public, health professionals, and policy makers to reduce the adverse outcomes associated with this disease.

In conclusion, osteoporosis and its related fractures constitute a major public health in LA and there are projections of an exponential increase in osteoporotic fractures in the region over the next decades. These trends show the need for timely and effective diagnosis of osteoporosis to reduce the disease burden in LA. The low self-awareness of osteoporosis and fracture risk among LA post-menopausal women and their health care providers, and limited access and utilization of bone densitometry and FRAX, are all important issues for immediate resolution. Health policy makers, insurance providers (both public and private), medical societies, employer organizations, hospitals, long-term care facilities, patients, and the general public should work to break the treatment inertia in osteoporosis by reevaluating the importance of osteoporosis prevention, treatment, and management as a health care priority. LA must overcome all these issues in order to achieve the goal of preventing unnecessary fractures.