Classification of Osteoporosis

Abstract

Osteoporosis is defined by low bone quality, strength and increased fracture risk. Primary and secondary osteoporosis are the two forms of osteoporosis classified on the basis of factors affecting the metabolism of bone. Primary osteoporosis develops as a result of aging or menopause-related bone demineralization. Type I/postmenopausal and type II/senile osteoporosis are two subtypes of primary osteoporosis. Secondary osteoporosis is due to pathological conditions and medications other than aging and menopause that lead to deprivation of bone mass and elevated fracture risk. Classification of osteoporosis based on BMD testing with DEXA devised by the World Health Organization utilizes T-score in BMD reporting of women in menopausal transition or postmenopause and men ≥ 50 years. Z-scores are preferred, while BMD reporting in premenopausal women, adults < 50 years of age, and children. BMD alone is not diagnostic of osteoporosis in men < 50 years. The Fracture Risk Assessment Tool Model (FRAX) is a software algorithm that incorporates significant predictors of fracture risk and BMD in individuals to predict the risk of fracture. FRAX predicts the “10-year probability of a major fracture (hip, clinical spine, humerus, or wrist fracture) and the 10-year probability of a hip fracture”.

Introduction

Osteoporosis is a highly prevalent metabolic bone disease affecting over 0.2 billion people worldwide. It is defined by reduced bone mineral density (BMD) and disrupted microarchitecture, causing skeletal fragility and fractures. It is more common in adults more than 50 years of age, and women are generally at a higher risk, especially postmenopausal women. As people age, the risk of developing osteoporosis increases. The absolute global prevalence of osteoporosis is difficult to calculate as it is a ‘silent’ pathophysiology until a fracture occurs [1–4]. Osteoporosis, being the most ubiquitous metabolic bone disease, represents an appreciable health issue globally. Osteoporosis is linked with increased morbidity and healthcare expenses and is a prime cause of fractures in the elderly. The prevalence and incidence of osteoporosis and its complications have significantly increased and will continue to increase in the coming years because of the global increase in the aging population and sedentary lifestyle habits. Early detection and initiation of appropriate management is warranted to reduce the healthcare burden of osteoporosis and its complications [1–5].

Osteoporosis is classified based on the etiology and severity of the disease (Fig. 1) [6–9]. Though various factors and pathological conditions cause osteoporosis, the common risk factors include age ≥ 50 years, female, low body mass index, Asian and ethnic white, family history, amenorrhea, delayed menarche and premature menopause, tobacco and alcohol abuse, deficiency of androgen, estrogen, calcium and vitamin-D, Sedentary lifestyle, lack of physical activities, prolonged immobilization or bed rest and intake of medications like oral glucocorticoids, insulin, anticonvulsants, thyroid supplements, anticoagulants and chemotherapeutic agents [10].

Fig. 1.

Flowchart showing the classification of osteoporosis

Etiological Classification

Osteoporosis is classified into two types based on the factors affecting bone metabolism.

Primary Osteoporosis

Primary osteoporosis, the most common form, develops due to aging or menopause-related bone demineralization. In primary osteoporosis, BMD decreases as the age increases [1, 8, 11]. Primary osteoporosis can be divided into two types (postmenopausal and senile).

Type I (Postmenopausal Osteoporosis)

Type I osteoporosis mainly affects the trabecular bone due to estrogen deficiency. Higher risk is seen among women than men [12]. In this type, vertebral and distal end radius fractures are more common. Type I osteoporosis is characterized by low circulating levels of total Vitamin D3 and net negative change in calcium levels due to reduced intestinal absorption and raised urinary excretion of calcium [12].

Type II (Senile Osteoporosis)

Type II osteoporosis is seen at age > 70 in both sexes. This type occurs as a result of the aging of trabecular and cortical bones and the resulting loss of bone mass and quality. Hip and pelvic bone fractures are more frequent in type II osteoporosis [12, 13].

Secondary Osteoporosis

Secondary osteoporosis can be defined as “osteoporosis due to conditions, diseases and medications other than aging and menopause that lead to low bone mass and elevated risk of fracture by directly or indirectly influencing bone metabolism or preventing the acquirement of peak bone mass in the younger population” [1, 13, 14]. Secondary osteoporosis can be localized or generalized. It can be due to various conditions, diseases, and medications [15–17]. The common conditions, diseases, and medications related to secondary osteoporosis can be read at https://doi.org/10.5152/eurjrheum.2016.048.

Classification of Osteoporosis Based on the Severity of the Disease

Bone mineral density (BMD) can be defined as the “quantity of calcium (calcium hydroxyapatite) per unit of bone”. BMD is an indirect indicator of bone quality and strength [18–20]. BMD is measured by various modalities like X-rays, ultrasonography, computed tomography, MR spectroscopy (MRS) and nuclear scans [21]. Dual-energy X-ray absorptiometry (DEXA) is the most prevalent in modern clinical practice. DEXA utilizes the “high sensitivity of calcium in absorbing X-rays to measure the relative amounts of bone and other soft tissue to calculate bone mineral content and, hence, density” [21, 22].

The patients are classified according to the site and method of measurement. DEXA measures BMD at various body sites (lumbar spine, hip and distal end radius). BMD is to be measured at both the total hip and posteroanterior (PA) spine (lumbar 1 to lumbar 4) in all patients. The BMD measurement at the hip can be done at four sites: the neck of the femur, trochanteric region, Ward’s triangle, and total hip. Among the four sites, the BMD measurement at the total hip should be preferred because it has reproducibility, good precision, and better correlation with fracture risk [23]. Though reliable and reproducible, the drawback of the lumbar BMD is that it is influenced by the artefacts. In certain populations, like patients with bilateral total hip replacements, lumbar spine surgeries like laminectomy, hyperparathyroidism, and morbidly obese individuals (who are beyond the prescribed weight limit of the DEXA table), BMD is to be measured at the 33% radius (also called 1/3 radius) according to the International Society for Clinical Densitometry (ISCD) [20]. Bone mineral density (BMD) is calculated in grams per cm² and is reported either as a T-score or Z-score based on the reference population used for comparison. The T-score is the “patient’s bone density compared with the BMD of control subjects at their peak BMD, and the Z-score reflects a bone density compared with patients matched for age and sex” [10, 24].

Classification of osteoporosis based on BMD testing with DEXA devised by the World Health Organization (WHO) is shown in Fig. 2 [10]. The classification is based on the T-score values obtained after BMD testing. T-score is defined as "patient measured BMD (in g/cm) value minus the reference BMD value (sex-matched, young adult reference population) divided by the reference standard deviation (SD) (sex-matched, young adult reference population)". The NHANES-III-recommended reference population for the calculation of T-score is the white females of 20–29 years [10]. Current evidence suggests that the most reliable BMD measurement site for predicting osteoporotic hip fracture risk is the total hip, and for observing the treatment response, it is the lumbar BMD.

Fig. 2.

The WHO classification criteria of osteoporosis T-score

Z-Score

Only during the second or third decade, the peak bone mass is achieved, depending on the site; hence, T-score cannot be used in children since T-score utilizes young adults as the reference population. The Z-score is “the number of standard deviations (SDs) from the mean bone mineral density of a healthy population of the same age, race and sex”. Z-score is obtained by subtracting the matched mean BMD from the measured BMD and dividing it by the matched SD. The ISCD suggests using ethnic- or race-adjusted Z-scores in children, premenopausal women, and adults < 50 years. Z-scores of ≤  − 2.0 SD are interpreted as “low or below the expected range of BMD for chronological age”, and >  − 2.0 SD is interpreted as “within the normal range” [11, 21].

Indications for Bone Mineral Density (BMD) Testing (ICSD)

BMD testing is indicated in patients when it is likely to impact management decisions. The ISCD recommends [20] that BMD testing should be performed for

1. Men ≥ 70 years and women ≥ 65 years

2. For women during the menopausal transition, post-menopausal women < 65 years, and men < 70 years, a BMD test is warranted if the patient has:

   • Low BMI.
   • Past history of fracture.
   • Intake of medications which causes bone loss (steroids, etc.).
   • Disease or pathological condition causing bone loss.

3. Adults having a past history of fragility fracture, disease, or pathological condition causing loss or low bone mass.

4. Adults being considered for pharmacologic therapy or taking high-risk medications causing low bone mass or bone loss.

5. To monitor treatment effects in patients receiving treatment.

6. Women discontinuing estrogen therapy.

Things to Consider While BMD Testing

BMD values can be influenced by

1. Positioning of the patient-decreased BMD (e.g., spinal rotation) or increased BMD (e.g., insufficient internal femur rotation).

2. Degenerative sclerotic changes in lumbar spine, ankylosing spondylitis, osteoporotic spinal compression fracture, etc. In those conditions, the affected level should be excluded from the analysis.

Pediatric Osteoporosis

Osteoporosis in children has been increasingly recognized in the past decade, but the data on the prevalence are inadequate. Genetics is the predominant determinator of bone mass and achievement of adult peak bone mass. Dietary factors and physical activities also play an important role. Bone strength in children can be compromised by both genetic and acquired bone disorders, leading to fractures. Most of the children with osteoporosis are mostly asymptomatic or present with bone pain. A child with a history of axial skeletal fractures or multiple fractures following a trivial injury should raise suspicion of osteoporosis. Pediatric osteoporosis can also be primary or secondary. The primary form can be genetic or idiopathic. Osteogenesis imperfecta, and Turner syndrome are the common genetic conditions associated. Secondary pediatric osteoporosis is due to chronic systemic illnesses, leukemia, hypogonadism, glucocorticoid therapy, anticonvulsant therapy, and malnutrition [25–28].

The cause of reduced bone mineral density in children can be idiopathic or due to increased bone resorption or inadequate new bone formation [26, 29]. The common conditions associated are shown in Table 1.

Table 1.

Causes of pediatric osteoporosis

Idiopathic	Increased bone resorption	Reduced bone formation
Sickle cell anemia and thalassemia Cystic fibrosis Long-term oral anticoagulants Celiac disease Type I diabetes Epilepsy Myelomeningocele Leukemias, especially acute lymphoblastic leukemia	Prolonged bed rest or immobilization Inflammatory bowel disease Juvenile Paget disease Idiopathic Juvenile Osteoporosis Rickets	Prolonged bed rest or immobilization Post burns Prolonged total parenteral nutrition Hepatic and renal osteodystrophy Medications (glucocorticoids, long-term inhaled corticosteroids)

Golden et al. [29]

According to the ICSD, pediatric osteoporosis can be defined as the combination of

1. “BMD Z-score ≤  − 2 SD and a clinically significant fracture history defined as the presence of either two or more long bone fractures before the age of 10 years or three or more long bone fractures at any age up to 19 years”. (or)

2. “One or more vertebral compression fractures occurring without high energy trauma or local disease irrespective of the BMD Z-score” [30, 31].

This definition distinguishes children with typical childhood fractures from a child experiencing fractures due to an underlying pathology. Given that fractures in childhood are common, pediatric osteoporosis should be diagnosed by the combination of BMD criteria and the clinical setting of the underlying disease or treatment [26, 32]. Unlike osteoporosis in adults, pediatric osteoporosis is not associated with increased mortality. The prognosis rests on the underlying etiology and severity of the disease activity. Failure in diagnosing and managing pediatric osteoporosis will cause low bone mass and quality, deformities, loss of function, reduced quality of life, and long-term complications [6, 26].

Idiopathic Juvenile Osteoporosis (IJO)

IJO is an uncommon type of primary osteoporosis in children. It is a self-limiting pathology with unknown etiology. IJO is defined by chronic back, hip and/or lower limb pain, and difficulties in ambulation. Compression fractures of the vertebrae and fractures of long bones are also seen in some cases. Usually, IJO is insidious in onset and starts before puberty (between age 8 and 14 years) in most cases. The symptoms may improve during puberty in some cases. Growth may be impaired during the acute phase of the disease which will be compensated later, and catch-up growth occurs, but rarely, IJO can result in permanent deformities like kyphoscoliosis or collapse of the rib cage. Typically, serum calcium and phosphorus levels are normal in IJO. Compared to other genetic causes of osteoporosis, in IJO, no positive familial history, extra-skeletal features, or growth impairment is seen. In some cases of IJO, heterozygous mutations of LRP5 have been implicated. Currently, IJO is diagnosed clinically and by exclusions of other causes, and there is no established medical or surgical treatment for IJO [32–34].

Fragility Fractures

Fragility fractures are the most significant complication of osteoporosis. Bone strength is determined by the combination of BMD and bone quality. Though BMD can be measured, bone quality is not measurable in a clinical setting except for the biochemical markers for the bone [35]. The risk of fracture is strongly correlated with bone quality and strength. The risk of fracture is indirectly proportional to the BMD. The conditions, diseases, and medications associated with a higher risk of fragility fractures can be read at https://doi.org/10.5152/eurjrheum.2016.048. The clinical fracture risk model, the FRAX tool [36], utilizes BMD and other clinical risk factors for fracture to predict the patient’s absolute fracture risk.

Fracture Risk Assessment Tool Model (FRAX)

A software algorithm incorporates significant predictors of fracture risk and BMD in individuals to predict the risk of fracture. FRAX outcome is based on “individual patient models that integrate the risks associated with clinical risk factors and BMD at the femoral neck”. It is intended to recognize patients who require treatment. FRAX predicts the “10-year probability of a major osteoporotic fracture (hip, clinical spine, humerus, or wrist fracture) and the 10-year probability of an osteoporotic hip fracture” [36, 37]. The tool can be accessed at https://frax.shef.ac.uk/FRAX/. The treatment for osteoporosis is indicated when the FRAX 10-year probability of a hip fracture is ≥ 3% or the risk for a major osteoporosis-related fracture is ≥ 20%[15]. FRAX is a useful prognostic tool for women who have had osteoporosis treatment in the past or present but not for patients who are receiving continuous treatment [36]. Furthermore, among women who are perimenopausal or in the early stages of menopause, it has a limited sensitivity for predicting fracture risk.

Summary

Osteoporosis is defined by low bone quality, strength, and increased fracture risk. Primary and secondary osteoporosis are the two forms of osteoporosis classified on the basis of factors affecting the metabolism of bone.

Primary osteoporosis develops as a result of aging or menopause-related bone demineralization. Type I/postmenopausal and type II/senile osteoporosis are two subtypes of primary osteoporosis. Secondary osteoporosis is due to pathological conditions and medications other than aging and menopause that lead to deprivation of bone mass and elevated fracture risk. Classification of osteoporosis based on BMD testing with DEXA devised by the World Health Organization utilizes T-score in BMD reporting of women in menopausal transition or postmenopause and men ≥ 50 years. Z-scores are preferred, while BMD reporting in premenopausal women, adults < 50 years of age, and children. BMD alone is not diagnostic of osteoporosis in men < 50 years. The Fracture Risk Assessment Tool Model (FRAX) is a software algorithm that incorporates significant predictors of fracture risk and BMD in individuals to predict the risk of fracture. FRAX predicts the “10-year probability of a major fracture (hip, clinical spine, humerus, or wrist fracture) and the 10-year probability of a hip fracture”.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Declarations

Conflict of Interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical Standard Statement

This article does not contain any studies with human or animal subjects performed by the any of the authors.

Informed Consent

For this type of study informed consent is not required.