Multidisciplinary clinical practice guideline for osteoporosis in Colombia: Evidence-based recommendations adapted to the national context

Abstract

Introduction

Osteoporosis is a skeletal disease characterized by low bone mineral density and deterioration of bone microarchitecture, which increases the risk of fractures. Between 2012 and 2018, 249,803 cases of osteoporosis were reported in individuals over 50 years of age in Colombia, with the incidence of fragility fractures doubling between 2015 and 2019. Despite its clinical and economic impact, over 80% of patients do not receive adequate treatment.

Objective

To develop an evidence-based clinical practice guideline (CPG) to improve the diagnosis, treatment, and follow-up of osteoporosis in Colombia, in order to patient care and the use of healthcare resources.

Methods

A multidisciplinary panel was assembled, including clinical specialists, guideline development experts, and patient representatives. Systematic reviews were conducted using electronic databases to build the evidence base, with methodological quality and certainty of evidence assessed using the GRADE approach. The evidence-to-decision framework was used to formulate 32 recommendations and 14 good practice points.

Results

The recommendations include diagnosis by bone densitometry and FRAX®, non-pharmacological treatment involving adequate nutrition, vitamin D, dietary and supplemental calcium as required, exercise, and fall prevention. These interventions are integrated with pharmacological treatment, which is selected based on fracture risk and the need for sequential therapy with bisphosphonates, denosumab, or osteoanabolic agents. The importance of a multidisciplinary approach, therapeutic adherence, and implementing fracture liaison services is emphasized.

Conclusions

Osteoporosis is an underdiagnosed and undertreated public health issue in Colombia. Implementing this CPG will help improve detection, optimize treatment, and reduce the associated disease burden.

Resumen

Introducción

La osteoporosis es una enfermedad esquelética caracterizada por una baja densidad mineral ósea y un deterioro de la microarquitectura ósea, lo que aumenta el riesgo de fracturas. En Colombia, entre 2012 y 2018 se reportaron 249.803 casos en mayores de 50 años, con una incidencia de fracturas por fragilidad que se duplicó entre 2015 y 2019. A pesar del impacto clínico y económico, más del 80% de los pacientes no recibe tratamiento adecuado.

Objetivo

Desarrollar una guía de práctica clínica (GPC) basada en la evidencia para mejorar el diagnóstico, el tratamiento y el seguimiento de la osteoporosis en Colombia, optimizando la atención y el uso de los recursos en salud.

Métodos

Se conformó un panel multidisciplinario compuesto por especialistas clínicos, expertos en el desarrollo de GPC y representación de pacientes. La base de evidencia se construyó a partir de revisiones sistemáticas realizadas en bases de datos electrónicas, con evaluación de calidad metodológica y de la certeza de la evidencia mediante el enfoque GRADE. A través del marco de evidencia a la decisión se formularon 32 recomendaciones y 14 puntos de buena práctica.

Resultados

Las recomendaciones incluyen diagnóstico mediante densitometría ósea y FRAX®, tratamiento no farmacológico con nutrición adecuada, vitamina D, calcio en la dieta y suplementación de ser necesaria, ejercicio y prevención de caídas. Estas intervenciones se integran con tratamiento farmacológico seleccionado según el riesgo de fractura y la necesidad de terapia secuencial con bifosfonatos, denosumab u osteoformadores. Se destaca la importancia del enfoque multidisciplinario, la adherencia terapéutica y la implementación de unidades de coordinación de fracturas.

Conclusiones

La osteoporosis es un problema de salud pública subdiagnosticado y subtratado en Colombia. La implementación de esta GPC contribuirá a mejorar la detección, optimizar el tratamiento y reducir la carga asociada a la enfermedad.

Introduction

Osteoporosis is a skeletal disease characterized by low bone mineral density (BMD) and a deterioration of bone microarchitecture, which increases bone fragility and the risk of fractures [1]. In Latin America, the incidence of hip fracture ranges from 40 to 362 cases per 100,000 inhabitants over 50 years of age, with an in-hospital mortality of up to 30% in the first year after fracture [2]. In Colombia, between 2012 and 2018, 249,803 cases were reported in people over 50 years of age, with a prevalence of 2440 per 100,000 inhabitants, mainly affecting women [3].

Fragility fractures have increased from 132 to 266 cases per 100,000 inhabitants between 2015 and 2019 [4]. It is estimated that in the year 2035 19.2% of Colombians will be over 60 years old, a figure that will reach 25.9% in 2050 [5,6], which will aggravate the burden of chronic diseases [4]. On the other hand, in Colombia in 2015 the direct cost of hip fracture was estimated at USD 4,428, USD 5855 for surgical vertebral fracture and USD 1196 for distal radius fracture [4], costs that increase with hospitalizations, surgeries, home care and disability, which represents a significant economic burden for the health system.

In addition, osteoporosis severely impairs quality of life. About 33% of hip fracture survivors are totally dependent at one year of the event [4]. This functional loss has a profound impact on the patients, their family, and the caregivers. Despite this, between 80% and 90% of patients do not receive adequate treatment [7]. Today, osteoporosis is not a public health priority and there are no structured primary prevention programs or national registries [8].

This Clinical Practice Guideline (CPG) seeks to integrate the best available evidence to optimize the diagnosis and treatment of osteoporosis in Colombia, reduce the burden of the disease, and improve the use of the health system resources [9].

Methodology

The Colombian Association of Osteoporosis and Mineral Metabolism (ACOMM) led this guideline, with a group of 13 specialists in geriatrics, endocrinology, rheumatology, family medicine, orthopedics, physiatry, sports medicine and gynecology, representing various regions of the country. EpiThink Health Consulting provided methodological support, and a patient representative participated throughout the process. All members declared possible conflict of interest in accordance with the Handbook on Health Technology Assessment [9], with no conflicts identified that compromised editorial independence.

The group defined the scope and objectives by consensus, formulating clinical questions in the format: Population, Intervention, Comparison and Outcome (PICO). Systematic reviews were conducted in Medline, Embase, Cochrane Library and LILACS, following the GRADE methodology [10]. Two independent reviewers assessed the quality of the evidence and resolved discrepancies by consensus, with results presented using a PRISMA flowchart [11].

Methodological quality was assessed using AGREE II for clinical guidelines [12], AMSTAR for systematic reviews [13] and the Cochrane risk of bias tool for clinical trials [14,15]. The certainty of the evidence was classified as high, moderate, low, or very low, based on the risk of bias, precision, consistency, and magnitude of the effect [16].

The recommendations were based on the balance between benefits and risks, patient preferences, feasibility of implementation and costs, and were structured with the Evidence to Decision framework [17]. Consensus was reached when at least 70% of participants gave scores of 4 or 5 on a Likert scale of 1–5. A total of 32 recommendations and 14 points of good practice were formulated, categorized as: strongly in favor (benefits outweigh risks), strongly against (risks outweigh benefits), conditionally in favor (benefits likely), and conditionally against (risks likely) [15].

The guideline was reviewed by the panel, externally evaluated, socialized with scientific societies, and peer-reviewed before publication.

Definitions and concepts

To facilitate the understanding and application of this guideline, the most relevant operational definitions in the context of osteoporosis (Table 1) and the main risk factors (Table 2) are presented.

Table 1.

Definitions in relation to osteoporosis.

Concept	Description
Diagnostic criteria (World Health Organization, modified to current evidence)	Normal: T-score ≥ −1.0 SD
	Low bone mass (osteopenia): T-score between −1.0 and −2.5 SD
	Osteoporosis: T-score ≤ −2.5 SD
	Severe or established osteoporosis: presence of fragility fracture [18]
Low bone mass	Z-score ≤ −2.0 in premenopausal women and men <50 years. Postmenopausal women with Z-score ≤ −2.0, consider secondary osteoporosis [19]
Classification in functions that affect bone metabolism	Primary osteoporosis: result of aging or menopause
	Secondary osteoporosis – due to diseases or medications that affect bone mass [20]
Classification of osteoporosis based on fracture risk	Osteoporosis with high risk for fracture
	Age >65 years with one of the following: previous fracture (>12 months), T-score ≤ − 2.5, or T-score between −1 and −2.5 with high risk in FRAX® [20]
	Very high-risk osteoporosis
	One of the following: recent (last 12 months), fractures during pharmacological treatment for osteoporosis or while taking drugs that cause bone damage, multiple fractures, very low T-score (<−3.5 SD), high risk of falls or history of falls with injuries, very high probability of fracture according to FRAX® located at the evaluation threshold for Colombian population [19]
Fragility fracture	Fracture after minimal trauma or even without apparent cause. The main fragility fractures include:
	Vertebral: often silent; they cause back pain, loss of height, and postural deformity. They are associated with a five-fold increased risk of new vertebral fracture and a two to three-fold increased risk of other fractures.
	Hip: in the proximal femur, they usually require surgery. They generate morbidity and mortality, functional loss, increased hospitalizations and excess mortality at one year
	Wrist: they occur in the distal radius or ulna
	Proximal humerus
Recent fracture	Any fracture that ocurred within the last 12 months is considred a recent fracture [19]
Indications for pharmacological treatment	Fragility fractures, regardless of bone mineral density
	T-score ≤ −2.5 SD
	Patients with osteopenia, when the result of the FRAX® evaluation for Colombia is within the treatment threshold
Antiresorptive drugs	Bisphosphonates and Denosumab
Bone forming drugs	Teriparatide and romosozumab

The panel assessed the evidence on hormone replacemtnt therapy and the selective estrogen receptor modulators. It was concluded that, due to its unestablished use in clinical practice and its cost-effectiveness, there is currently insufficient support to generate recommendations in this regard.

SD: Standard Deviation; FRAX: Fracture Risk Assessement Tool.

Table 2.

Risk factors for osteoporosis.

Grouping	Risk factors
Genetic and constitutional	Advanced age, female sex, White or Asian race, body mass index <19 kg/m^2, low peak bone mass, parental history of fragility hip fracture
Reproductive	Early menopause, delayed puberty, estrogenic decrease due to irregular cycles, infertility of hormonal origin, prolonged contraception with progesterone
Nutritional	Anorexia nervosa, caloric insufficiency at puberty, accelerated weight loss at any age, calcium or vitamin D3 deficiency
Lifestyle	Smoking, alcohol (>3 doses/day), sedentary lifestyle or immobilization
Drugs	Glucocorticoids at doses ≥ 5 mg/day of prednisolone >3 months, anticonvulsants, proton pump inhibitors (>1 year), therapies that reduce gonadal steroids, chemotherapy or immunosuppressive agents, chronic use of long-acting medroxyprogesterone acetate, thyroxine in supraphysiological doses, lithium, PPAR-gamma agonists, anticoagulants, protease inhibitors or serotonin reuptake inhibitors
Diseases	Endocrine: type 1 and type 2 diabetes mellitus, hyperthyroidism, hyperparathyroidism, hypogonadism, hypophosphatasia, Cushing's syndrome
	Rheumatological: rheumatoid arthritis, spondiloarthritis
	Malabsorption or malnutrition syndromes: Crohn's disease, hemochromatosis, celiac disease, cystic fibrosis, and bariatric surgery
	Renal: renal tubular acidosis, chronic kidney disease (stages 4 and 5) and kidney transplantation
	Cancer and hematological neoplasms such as multiple myeloma
	Other: human immunodeficiency virus (HIV) infection, chronic obstructive pulmonary disease, hemophilia, liver cirrhosis, primary biliary cholangitis.

Recommendations

General principles for the approach to osteoporosis

• •

  The recommendations in this guide provide general guidance on the approach to osteoporosis, but they should be adapted to each patient.

• •

  Management should be comprehensive and multidisciplinary, especially in cases of very high risk and high risk of fracture.

• •

  Pharmacological treatment should be maintained for as long as necessary for its effectiveness and only discontinued if the risks outweigh the benefits.

• •

  Decisions should consider, in addition to the risk-benefit balance, the preferences and circumstances of the patient and their environment to promote adherence to treatment.

• •

  It is key to identify and correct the causes of non-adherence to treatment, addressing factors related to the patient, the treatment and the health system.

Diagnosis and evaluation of osteoporosis

The evaluation and intervention thresholds in the Colombian population are presented in Fig. 1. The algorithm for the diagnosis and evaluation of primary postmenopausal and age-associated osteoporosis is presented in Fig. 2.

Figure 1.

Thresholds for evaluation and intervention with FRAX® for the Colombian population.

Source [8].

Figure 2.

Algorithm for the diagnosis and evaluation of primary postmenopausal and age-associated osteoporosis.

SD: standard deviation; BMD: bone mineral density; DXA: dual-energy X-ray central absorptiometry; MOF: major osteoporotic fracture; FRAX®: Fracture Risk Assessment Tool; REMS: bone densitometry by radiofrequency echografic multispecrometry; Rx: radiograph; TBS: Trabecular Bone Score; VFA: vertebral fracture assessment.

¹ Particulary in people with chronic kidney disease, rheumatoid arthritis, type 2 diabetes mellitus or under long-term glucocorticoid treatment.

² In patients with T-score < −1 SD, associated at least with one of the following: woman ≥ 70 years of age, men ≥ 80 years of age, height loss > 4 cm, hyperkyphosis, history of undocumented vertebral fracture, consumption of glucocorticoids (25 mg/day of prednisolone or its equivalent) for more than three months or in whom it is going to start it.

³ In cases of hyperkyphosis or pain in the thoracic or lumbar spine lasting more than 15 days without apparent cause.

DXA bone densitometry and risk assessment by FRAX®

Good practice point 1. DXA is recommended in:

Women ≥ 65 years and men ≥ 70 years (screening)

Women < 65 years and men < 70 years with any of the following risk factors:

• •

  BMI < 19 kg/m²

• •

  Previous fragility fracture

• •

  Prolonged use of medications that affect bone mass

• •

  Diseases that generate bone loss

Good practice point 2. Central DXA should include measurement of the lumbar spine, femoral neck, and total hip. For the diagnosis, the lowest T-score between the femoral neck or total hip is chosen.

Good practice point 3. If DXA is not available, FRAX® allows the estimation of the risk of major osteoporotic fracture, placing it at the intervention threshold for the Colombian population.

Good practice point 4. The FRAX® categorizes the risk of fracture and is complementary for the therapeutic decision.

Diagnostic tools should be selected based on availability and clinical applicability. The easily accessible and low-cost FRAX® allows to detect high-risk cases for timely intervention in patients without prior treatment, and is useful for the estimation of fracture risk in those without access to DXA, although it does not incorporate the risk of falls or adequately adjust for the impact of certain medications such as glucocorticoids [8]. Due to its limitations, it is considered a complementary tool in decision-making in the evaluation of patients with osteoporosis. Future research should evaluate the FRAX® Plus and the proximal hip axis length index in postmenopausal women [21].

DXA is the reference method according to the International Society of Clinical Densitometry [22] and the American College of Radiology [23]. FRAX® with BMD has a good discriminative performance in predicting any fracture due to osteoporosis (area under the curve AUC 0.72) [24].

Bone densitometry by radiofrequency echographic multi spectrometry

Recommendation 1. Radiofrequency echographic multi spectrometry (REMS) is suggested as an alternative to DXA for the diagnosis of osteoporosis in adults with obesity, kidney disease, bone deformities, type 2 diabetes, or pregnancy.

(Conditional in favor, moderate certainty)

Recommendation 2. Hip REMS is recommended to assess bone mass in pregnant women.

(Strong in favor, moderate certainty)

REMS has emerged as a valid alternative, showing 90% concordance with DXA in recent studies [25]. This non-ionizing technology allows to evaluate BMD in patients in whom DXA is not reliable [26,27]. The REMS-based T-score has demonstrated the ability to successfully assess BMD with similar values, compared to DXA in populations with type 2 diabetes mellitus, kidney disease, and rheumatoid arthritis [28,29]. In addition, studies in Mexico and Brazil confirm its usefulness in populations without access to DXA [30,31].

Quantitative ultrasound

Recommendation 3. It is suggested not to use quantitative ultrasound (QUS) (calcaneus, phalanx, tibia) for the diagnosis or follow-up of osteoporosis.

(Conditional against, low certainty)

QUS does not measure BMD directly, which generates discrepancies with DXA. Although it has been suggested that screening with FRAX® and QUS before DXA could be more cost-effective in adults over 65 years of age, its effectiveness is limited [32,33]. Currently, there is not enough evidence to recommend its use as a screening tool [33].

Bone quality assessment: Trabecular Bone Score

Recommendation 4.Trabecular Bone Score (TBS) is recommended during DXA for adults with osteopenia or osteoporosis.

(Strong in favor, moderate certainty)

Recommendation 5. TBS along with FRAX® is recommended in adults with chronic kidney disease, rheumatoid arthritis, type 2 diabetes mellitus, or on long-term treatment with glucocorticoids.

(Strong in favor, moderate certainty)

Assessment of bone quality is key in the prediction of fracture risk. TBS complements DXA, providing information on bone microarchitecture and improving the prediction of fracture risk. According to observational studies and expert consensus, TBS, along with BMD and FRAX®, are useful for adjusting the FRAX® fracture probability in postmenopausal women and in men over 50 years of age. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF) recommend the use of TBS if FRAX® indicates an intermediate risk of fracture, in women aged 65 years or older and in men aged 70 years or older for routine monitoring of bone health. In addition, TBS is recommended along with BMD in cases of fragility fracture, secondary osteoporosis, or if there is a risk factor for low bone mass [34,35].

Vertebral fracture assessment

Recommendation 6. Vertebral fracture assessment (VFA) is suggested in adults with T-score ≤ -2.5 in the spine or hip, or fragility fracture.

(Conditional in favor, low certainty)

Recommendation 7. VFA is suggested in adults with a T-score ≤ −1.0 SD and at least one of the following:years women ≥ 70 years, men ≥ 80 years, height loss >4 cm, report of undocumented vertebral fracture, prolonged use of glucocorticoids or hyperkyphosis.

(Conditional in favor, low certainty)

Vertebral morphometry allows for the quantitative evaluation of vertebral fractures, an important predictor of future fractures. A meta-analysis of more than 25,000 women evaluated with VFA by DXA showed a prevalence of 28% of vertebral fractures in asymptomatic women, increasing to 41% in women ≥ 65 years, many of them without a previous diagnosis of osteoporosis [35]. The VFA has demonstrated high sensitivity (93%) and specificity (93%) for evaluating vertebral fractures compared to conventional radiography in postmenopausal women and men aged 50 years and older [36]. For this reason, scientific societies such as ISCD and NOGG recommend its use in adults with very low T-score and additional risk factors [36,37].

Fragility score

Recommendation 8. It is suggested to use the Fragility Score by REMS to predict fractures in the spine and femoral neck in osteoporosis.

(Conditional in favor, moderate certainty)

The Fragility Score obtained by REMS, a non-ionizing tool for estimating bone fragility, has shown greater predictive capacity for fragility hip fractures than DXA T-scores, with AUC values ​​of 0.735 in women and 0.758 in men (prospective cohort n = 1989) [38]. Although the evaluations did not consider other clinical risk factors, their use could improve the early identification of people at high risk and prevent the first fracture.

Other images and laboratories

Thoracolumbar spine X-ray

Recommendation 9. Lateral radiograph of the thoracolumbar spine is suggested in adults with osteoporosis and loss of height > 4 cm, hyperkyphosis, or dorso-lumbar pain for more than 15 days with no apparent cause.

(Conditional in favor, low certainty)

Recommendation 10. If VFA is not available, it is suggested to take an X-ray in adults with a T-score < -1.0 SD and at least one of the following: women ≥ 70 years, men ≥ 80 years, height loss > 4 cm, undocumented vertebral fracture, prolonged use of glucocorticoids, or hyperkyphosis.

(Conditional in favor, low certainty)

Evidence regarding the use of radiographs in osteoporosis is very limited. Routine plain radiographs are generally not recommended for the diagnosis of osteoporosis, as osteopenia is only evident after bone loss exceeding 30% [39]. The recommendations are aimed at taking lateral radiographs of the dorsolumbar spine in patients with osteopenia and risk factors for fracture.

Bone markers

Recommendation 11. The routine use of bone markers is not recommended in primary osteoporosis.

(Strong against, moderate certainty)

Bone markers, of bone formation or resorption, are byproducts produced from the bone remodeling process, indicative of the rate of bone turnover [40]. Some bone markers, such as the type 1 procollagen amino-terminal extension peptide (P1NP), the carboxy-terminal telopeptide of type 1 collagen (CTX) and the amino-terminal collagen telopeptide (NTX) have been associated with lower BMD or with fracture in some subpopulations [41]. Although they may contribute to patient assessment and improve the detection of some causes of secondary osteoporosis [42], the usefulness of bone turnover markers in the management of osteoporosis is currently unclear.

Differential diagnosis: basic and specialized laboratories

Good practice point 5. In the study of osteoporosis, the hemogram and erythrocyte sedimentation rate (ESR) are useful to rule out secondary causes such as multiple myeloma or leukemias.

Good practice point 6. The total serum calcium should be measured in all patients with osteoporosis. In cases of hypoalbuminemia, correct the calcium value according to albumin.

Good practice point 7. It is necessary to evaluate the levels of 25-hydroxyvitamin D and creatinine (to calculate the glomerular filtration rate, CKD-EPI formula) before starting drug treatment.

Good practice point 8. Phosphorus measurement is reserved for cases related to disorders of phosphocalcic metabolism.

Basic examinations make it possible to rule out secondary causes of osteoporosis and detect comorbidities with bone impact. In Colombia, the high prevalence of hypovitaminosis D, justifies the measurement of 25 OH vit D levels before treatment. The target serum level of 25 OH vitamin D in osteoporosis is 30 ng–40 ng/mL and serum levels should be monitored at least twice a year during treatment. In addition, the glomerular filtration rate (by CKD-EPI) must be calculated, as values < 35 mL/min/1.73 m² contraindicate certain drugs. Specialized studies should be requested only when there is a clinical suspicion that justifies it.

Treatments for osteoporosis

Once the diagnosis of primary osteoporosis is established, management includes pharmacological and non-pharmacological interventions, according to the algorithm in Fig. 3.

Figure 3.

Algorithm for the treatment of primary postmenopausal and age-associated osteoporosis.

SD: standard deviation; MOF: major osteoporotic fracture; Fx: fracture; GFR: glomerular filtration rate; Vit: vitamin.

1. Liver failure, obesity, bariatric surgery, or malabsorption syndrome.

2. Except in people with a history of skin cancer, malignant melanoma, or systemic lupus erythematosus.

3. Optional in high fracture risk.

Non-pharmacological treatment

Calcium and vitamin D

Recommendation 12. Iti s recommended to consume 1200 mg daily of calcium from the diet in adults over 50 years of age with osteoporosis.

(Strong in favor, moderate certainty)

Recommendation 13. Calcium and vitamin D supplementation is recommended in adults with osteoporosis, regardless of fracture risk, as a complement to pharmacological treatment.

(Strong in favor, moderate certainty)

Recommendation 14. Vitamin D3 supplementation is recommended in adults with osteoporosis, especially in those over 65 years of age or with vitamin D deficiency.

(Strong in favor, moderate certainty)

Recommendation 15. Calcifediol supplementation is recommended as first-line treatment in osteoporosis concomitant with liver failure, obesity, bariatric surgery, malabsorption, or institutionalized elderly adults at very high risk of fracture.

(Strong in favor, moderate certainty)

The combination of calcium and vitamin D, which has been widely evaluated [43–48], improves total BMD of the lumbar spine and femoral neck, and significantly reduces the occurrence of hip fractures, especially in elderly patients, with low body weight or high risk of fractures [49]. Evidence in women over 60 years of age suggests that calcium with vitamin D supplementation should accompany pharmacological treatment of osteoporosis [50]. Serum levels should be monitored at the start of treatment and at least twice a year during treatment. The minimum effective recommended dose of calcium is 1200 mg and of vitamin D ≥ 800 IU [47], associated with 13% and 19% lower risk of fractures and falls, respectively [51]. Intermittent or single doses are discouraged due to their low efficacy [52], and the use of calcitriol as part of treatment is not recommended due to the lack of evidence in the reduction of non-vertebral or hip fractures and the associated risk of hypercalcemia or hypercalciuria.

Calcium and vitamin D formulations, included in the Health Benefits Plan and low-cost, have good acceptability; problems of adherence due to intolerance or polypharmacy should be evaluated and managed individually.

Probiotics, diet and lifestyle

Good practice point 9. The consumption of foods fortified with vitamin D should be guaranteed in postmenopausal women.

Good practice point 10. The diet in people with osteoporosis should be balanced and include protein, magnesium, vitamin K2 and vitamin E.

Good practice point 11. Routine measurement of micronutrients or additional micronutrient supplementation is not required in people with osteoporosis.

Good practice point 12. The diet of people with osteoporosis should incorporate foods that provide probiotics and reduce ultra-processed foods.

Good practice point 13. People with osteoporosis should limit alcohol consumption and quit smoking.

Good practice point 14. Direct sun exposure should be done three times a week for 15 min, avoiding exposing the face. This does not apply to people with a history of skin cancer, malignant melanoma, or systemic lupus erythematosus.

The recommended dietary intake of calcium for women over 50 years of age and men over 70 years of age in Colombia is 1000 mg to 1200 mg [54]. To determine the average daily calcium intake and the requirement by age, the IOF calcium calculator is recommended.

(Available at https://www.osteoporosis.foundation/educational-hub/topic/calcium-calculator).

Regarding the diet, daily protein consumption is key to maintaining muscle mass and bone density [53,54]. Probiotics, meanwhile, promote mineral absorption and bone health, and are recommended as part of the diet, while supplements, which appear to slow bone resorption in postmenopausal women, require further study [55]. Excessive alcohol consumption, smoking, and a sedentary lifestyle increase the risk of fractures, so adopting healthy lifestyle habits is advised.

Exercise

Recommendation 16. Exercise prescription is recommended for adults with osteoporosis (with or without fracture), under the guidance of specialists in sports medicine or physical medicine and rehabilitation.

(Strong in favor, certainty of evidence: moderate)

Recommendation 17. It is recommended to plan the prescribed exercise considering intensity, frequency, type, variation and progression.

(Strong in favor, certainty of evidence: moderate)

Recommendation 18. It is recommended that adults with osteoporosis do exercise at least 3 days a week continuously and with regular check-ups.

(Strong in favor, certainty of evidence: moderate)

Recommendation 19. It is recommended that adults with osteoporosis combine strength, balance, aerobic, and flexibility exercises.

(Strong in favor, certainty of evidence: moderate)

Recommendation 20. It is recommended that exercise in adults with osteoporosis be supervised by qualified personnel, particularly in those at high risk or very high risk of fracture.

(Strong in favor, certainty of evidence: moderate)

Recommendation 21. It is suggested to assess the risk of falls (modified Downton scale) in adults with osteoporosis and adjust interventions according to the risks identified.

(Conditional in favor, certainty of evidence: moderate)

Evidence consistently supports multicomponent exercise for the treatment of osteoporosis. Exercise improves BMD, muscle strength, balance, functionality, and quality of life. Combining resistance, balance, and flexibility exercises has shown evidence of reducing falls and fractures, especially in high- and very-high-risk patients [56,57]. The effectiveness of exercise depends on the intensity and adherence [58] and the benefits appear after six months of supervised practice. On the other hand, exercise is considered a safe activity and should be encouraged even in people at high risk or previous fractures, to avoid inactivity and preserve bone strength and quality of life.

Pharmacological treatment

Bisphosphonates

Recommendation 22. The use of alendronate, risedronate, or zoledronic acid is recommended as first-line treatment in adults at high risk of fracture.

(Strong in favor, moderate certainty)

Recommendation 23. The preferential use of zoledronic acid is recommended in adults with osteoporosis under 75 years of age, after hip fracture, poor adherence, oral intolerance or polypharmacy.

(Strong in favor, moderate certainty)

Recommendation 24. The use of ibandronate as an alternative is suggested in adults younger than 65 years with T-score < - 2.5 SD in the spine and ≥ -1 SD in the hip.

(Conditional in favor, moderate certainty)

The available evidence consistently shows the effect of bisphosphonates on improving BMD and reducing vertebral and non-vertebral fractures in women and men [59–69]. Alendronate is the most effective in secondary prevention [68], while zoledronic acid is superior in vertebral fractures [60]. In real-world studies, bisphosphonates have been shown to reduce the risk of mortality, with no significant increase in serious adverse events [69].

The most frequent adverse effects of oral bisphosphonates, which include dyspepsia and esophagitis, are avoidable with dose adjustments and recommendations on drug intake (with 240 mL of water and remaining upright for 30−60 min) [70]. Serious adverse events such as atypical femoral fracture and medication-related osteonecrosis of the jaw (MRONJ) are very rare [71] (atypical fracture in 1.1% of femoral fractures and risk of MRONJ ≤ 0.02% with intravenous zoledronate and ≤ 0.05% with oral bisphosphonates [72]. It is recommended to maintain good oral health through education, prevention, and management of dental problems [73].

Denosumab

Recommendation 25. Denosumab is recommended in adults of any age with osteoporosis at high risk of fracture, in patients over 75 years of age, T-score < - 2.5 in the hip, GFR < 35 mL/min, or contraindication of bisphosphonates.

(Strong in favor, moderate certainty)

Evidence supports the effect of denosumab in improving BMD and reducing the risk of falls and osteoporotic fractures, including hip and spine fractures [74–81]. Studies such as FREEDOM and other sub-analyses support its effectiveness, regardless of the age [82,83] and the renal function status [84]. Abrupt discontinuation of denosumab increases the risk of vertebral fractures, so its continuity or the transition to another antiresorptive agent must be ensured. It is crucial to educate physicians and dentists to avoid barriers to adherence and ensure continuity of treatment with this medication.

Bone forming agents

Recommendation 26. Teriparatide or romosozumab is recommended in adults with severe vertebral fracture (Genant grade III), or ≥ 2 vertebral fractures of any severity, or T-score ≤ -3.5

(Strong in favor, moderate-high certainty)

Evidence supports the use of teriparatide and romosozumab in primary osteoporosis and very high risk of fractures. Teriparatide increases BMD in the spine, hip, and femoral neck, reduces vertebral fractures and pain compared with placebo and antiresorptives, especially in postmenopausal women with multiple vertebral fractures [85–87]. In men, it also significantly increases the lumbar and femoral neck BMD [77]. Romosozumab, for its part, significantly reduces vertebral, non-vertebral and clinical fractures, as well as the risk of falls, and increases BMD in the spine, hip and femoral neck at 12 months [88]. Regarding safety, adverse events are generally similar to those of other treatments for osteoporosis [89]. However, with romosozumab, it is necessary to monitor for serious cardiovascular events [90,91].

Sequential therapy

Recommendation 27. From the beginning of treatment, sequential therapy should be planned: bone forming → antiresorptive, high-potency bisphosphonate → denosumab, denosumab, → high-potency bisphosphonate.

(Conditional in favor, moderate-high certainty)

The use of sequential therapy in osteoporosis improves BMD and maintains the benefit in reducing the risk of fracture in the long term [75,92–96]. The suggested planned transitions include:

• •

  After bone-forming therapy: upon completion of treatment with teriparatide (24 months) or romosozumab (12 months), continue treatment with a potent antiresorptive drug to consolidate and maintain the gains in BMD.

• •

  After high-potency bisphosphonates: the transition to denosumab may result in additional increases in BMD, especially in patients who do not achieve therapeutic targets with bisphosphonates.

• •

  After therapy with denosumab: avoid abrupt discontinuation due to rebound effect with rapid bone loss. It is recommended to apply zoledronic acid strictly six months after the last dose of denosumab.

These strategies, supported by studies and clinical guidelines, make it possible to consolidate treatment, prevent relapses, optimize long-term results and reduce costs, as long as the continuity of treatment is guaranteed and the patient is adequately informed about its benefits and possible adverse effects. The recommendations for the continuity of treatment in osteoporosis are schematized in Fig. 4.

Figure 4.

Continuity of treatment in osteoporosis.

ALN: alendronate; IBN: ibandronate; SD: standard deviation; Dmab: denosumab; BMD: bone mineral density; DXA: dual-energy X-ray absorptiometdry; RIS: risedronate; RZB: romosozumab; TPT: teriparatide; ZOL: zoledronic acid.

In Colombia, teriparatide is approved for a maximum of 24 months (INVIMA, September 26, 2024), although prolonged use may be required in high-risk patients.

Follow-up of the treatment and the disease

Biomarkers

Recommendation 28. Routine measurement of bone turnover markers is not recommended in adults with primary osteoporosis.

(Strong against, moderate certainty)

Recommendation 29. It is suggested to measure s-CTX in adults with osteoporosis and suspected therapeutic failure, poor adherence, secondary osteoporosis, or after discontinuing denosumab.

(Conditional in favor, moderate certainty)

Recommendation 30. It is not recommended to use bone markers to assess the risk of maxillary osteonecrosis in adults with osteoporosis.

(Strong against, moderate certainty)

Evidence on the use of bone markers in the follow-up of osteoporosis treatment is limited. Certain elevated biomarkers have been associated with lower BMD and increased risk of fracture before treatment, and their reduction, especially of bone-specific alkaline phophatase [97] and osteocalcin [98], has been linked to a lower risk of fractures in treated patients. An s-CTX level higher than 1.0 ng/mL can be considered an indicator of increased bone resorption.

Currently, biomarkers, especially s-CTX, can be useful in the study of secondary osteoporosis, when loss of adherence to treatment is suspected, for the evaluation of therapeutic failure, or in the monitoring of bone turnover after discontinuation of denosumab [97,99]. However, its routine use is limited by the high variability between patients and more research is needed to define its predictive value in clinical practice.

Follow-up images

Recommendation 31. DXA evaluation is recommended every 2 years in adults with osteoporosis undergoing treatment, except with romosozumab, which is evaluated one year after completing treatment.

(Strong in favor, moderate certainty)

Recommendation 32. Radiographic or morphometric follow-up is suggested in adults with osteoporosis who present therapeutic failure or height loss.

(Conditional in favor, low certainty)

Follow-up with DXA should have defined clinical objectives and be performed at individualized intervals according to age, sex, fracture risk, and previous treatment [100–102]. All approved drugs stabilize or increase BMD in the spine and hip within one to three years, although there is no standardization of radiographic or morphometric follow-up. A more frequent periodicity is useful in patients with greater expected loss of bone mass or very low BMD. Interpretation requires knowing the minimum significant change and using the same DXA equipment to avoid bias [103] (this does not apply to REMS).

Considerations for the implementation of the Guide

Osteoporosis is an underdiagnosed and undertreated disease worldwide. Less than 20% of affected people receive a diagnosis and only 35% start treatment, even after a fracture [104]. In Colombia, only a third of patients with osteoporosis receive supplements of calcium, vitamin D or pharmacological treatment [105], while post-fracture pharmacological management varies between 10% and 58%, depending on the existence of secondary prevention programs [7,105]. On the other hand, access to tools for osteoporosis assessment varies regionally, and technical standardization is required to improve accuracy.

Strengthening organized strategies is essential. Fracture Liaison Services (FLS), or Fracture Coordination Units, have been shown to reduce the risk of new fractures, mortality, and healthcare costs [106,107]. In the country, a FLS program achieved an adherence rate of 74.6% per year, with a low incidence of new fractures [108]. Another key strategy is the orthogeriatric model, which improves diagnosis and treatment, reduces in-hospital stay and mortality, and decreases the incidence of delirium in patients with hip fracture [109,110]. However, less than half of patients maintain treatment beyond six months, which highlights the need to strengthen these comprehensive and multidisciplinary care strategies.

This guideline seeks to support medical decision-making with the best available evidence, serving as a tool to optimize disease management, without replacing clinical judgment. Given the aging of the Colombian population and the growing burden of osteoporosis, the implementation of the guide is a priority. To ensure its validity and applicability, it is essential to make periodic updates and conduct local economic studies that support the proposed interventions. This will allow us to optimize the approach to adults with osteoporosis, ensuring a positive impact on the bone health of the population and on the sustainability of the health system.

CRediT authorship contribution statement

This document has been prepared by the Colombian Association of Osteoporosis and Mineral Metabolism. Geraldine Altamar-Canales, Daniel G. Fernández-Ávila, Miguel Ángel González-Reyes, Francisco Bernardo Linares-Restrepo, Adriana Medina-Orjuela and Francisco Oscar Fernando Rosero-Olarte participated in the conception, definition of scope and selection of topics for the Clinical Practice Guideline, as well as in the thematic direction and validation of the evidence obtained. All authors contributed to the critical review of the evidence and to the discussions that underpinned the formulation of the final recommendations. Likewise, all authors revieewed and approved the final version of the manuscript and the algorithms.

Future update

The CPG will be updated within a maximum of five years, or sooner if new evidence that modifies its recommendations arises.

Funding

This CPG was funded and developed by the Colombian Association of Osteoporosis and Mineral Metabolism (ACOMM). The pharmaceutical industry supported its dissemination, without intervening in its contents.

Acknowledgements

We thank Gina Ochoa, director of the Fundación LICAR, for her participation as a representative of the patients.