Significance of achilles Ultrasonometer in the precised Diagnosis and Assessment of Osteoporosis

 

Praveen Kumar.T¹, Dhanapal C K², M. Sudhakar³, Satyabrata Bhanja⁴, Ayyagari Akhila⁵, PDSS Prakash⁶

^1,3,4,5Department of Pharmacy Practice, Malla Reddy Hospital, Secunderabad, Telangana State

²Department of Pharmacy, Annamalai College of Pharmacy, Annamalai University, Annamalai Nagar, Chidambaram

 

ABSTRACT:

Osteoporosis is a disease that is characterized by low bone mass, deterioration of bone tissue, and disrup­tion of bone microarchitecture. The diagnosis and clinical management of osteoporosis relies mainly on the measurement of bone density, because low bone density is associated with future risk of atraumatic and fragility fractures. During the last three decades several techniques have been developed for the measurement of bone density which are safe, precise, and accurate. Most of these techniques used some form of ionizing radiation (x-rays), and the measurement obtained is based on the attenuation of a beam of energy as it passes through bone and soft tissues. The use of acoustic energy in the form of ultrasound wave has been suggested as possible choice for the assessment of bone integrity and to determine bone's response to mechanical loads to predict the risk of fracture. Transmission mode uses two transducers, one acting as transmitter and the other as a receiver of the ultrasound wave. Achilles Express bone Ultrasonometer is used to evaluate bone status by measuring stiffness index in the heel. Measurement of BUA (Broadband Ultrasound Attenuation) involves sending a broadband ultrasound pulse through the bone and measuring the reduction in intensity at different frequencies. Stiffness Index which represents bone mineral density, combines BUA and SOS (Speed of Sound) into a single clinical measure that has a lower precision error than either variable alone. The T-score is the most significant parameter for the assessment of osteoporosis. It is concluded that QUS can be effectively used to study the bone mineral loss and QUS clearly distinguishes between normal and osteoporotic subjects and can be a useful index in clinical management of osteoporosis. Thus Achilles Express Ultrasonometer is a reasonable and accurate screening tool to detect low BMD.  

 

KEYWORDS: Osteoporosis, T-score, Z-score, Broadband Ultrasound Attenuation (BUA), Achilles Express bone Ultrasonometer.

 

 

INTRODUCTION:

Osteoporosis is a disease that is characterized by low bone mass, deterioration of bone tissue, and disrup­tion of bone microarchitecture: it can lead to compromised bone strength and an increase in the risk of fractures ¹. Osteoporosis is the most common bone disease in humans, representing a major public health problem. Osteoporosis is a risk factor for fracture. Osteoporosis affects an enormous number of people, of both sexes and all races, and its prevalence will increase as the population ages. It is a silent disease until fractures occur, which causes important secondary health problems and even death². It was estimated that the number of patients worldwide with osteoporotic hip fractures is more than 200 million ³.  Osteoporosis-related fractures are associated with sub­stantial pain, suffering, disability, and possibly even death for the affected patients. Further, increasing longevity has resulted in an increasing number of senior citizens globally; life expectancy at present is ~67 years in India and is expected to increase to 71 years by 2025 and to 77 years by 2050. Further, ~10% of the Indian population is older than 50 years at present; however, these figures are likely to go up to 34% by 2050. Thus, increasing longevity and a greater proportion of the Indian population over the age of 50 years are likely to result in an increased number of people affected by osteoporosis. In 2013, estimates suggested that ~50 million people in India had T-scores of less than -1.⁴ It was estimated that around the age of 50 years, the probability of having a hip fracture in the remaining lifetime was 3.5% in men and 14.6% in women⁵. Thyroid hormones impact growth, development, metabolism⁶, bone and heart physiology⁷, so hypothyroidism effect on numerous metabolic processes and in all tissues of the body and so every tissue in the body is affected to a greater or lesser extent in thyroid hormone deficiency and the cardiovascular system is the most sensitive one and hypothyroidism revealed to be significantly associated with female gender and old age⁸.

 

Bone tissue is continuously lost by resorption and rebuilt by formation; bone loss occurs if the resorption rate is more than the formation rate. The bone mass is modeled (grows and takes its final shape) from birth to adulthood: bone mass reaches its peak (referred to as peak bone mass (PBM)) at puberty; subse­quently, the loss of bone mass starts. PBM is largely determined by genetic factors, health during growth, nutrition, endocrine status, gender, and physical activity. Bone remodeling, which involves the removal of older bone to replace with new bone, is used to repair microfractures and prevent them from becoming macro fractures, thereby assisting in maintaining a healthy skeleton. Menopause and advancing age cause an imbalance between resorption and formation rates (resorption becomes higher than absorption), there­by increasing the risk of fracture. Certain factors that increase resorption more than formation also induce bone loss, revealing the microarchitecture. Individual trabecular plates of bone are lost, leaving an architec­turally weakened structure with significantly reduced mass; this leads to an increased risk of fracture that is aggravated by other aging-associated declines in functioning. Increasing evidence suggests that rapid bone remodeling (as measured by biochem­ical markers of bone resorption or formation) increases bone fragility and risk of fracture. There are factors associated with an increased risk of osteoporosis. These in­clude general factors that relate to aging and sex steroid deficiency, as well as specific risk factors such as use of glucocorticoids (which cause decreased bone formation and bone loss), reduced bone quality, and disruption of microarchitectural integrity. Fractures result when weakened bone is overloaded, often by falls or certain daily chores ⁹.

 

Classification:

Osteoporosis can be classified into two main groups by considering the factors affecting bone metabolism:

-Primary osteoporosis

-Secondary osteoporosis

-Primary osteoporosis can also be divided into two subgroups:

 

Involutional Osteoporosis Type I:

It is also known as postmenopausal osteopo­rosis, caused by the deficiency of estrogen, mainly affecting the trabecular bone; therefore, women are more susceptible to osteoporosis than men, as evident by a men/women ratio of 4/5.7.

 

Involutional Osteoporosis Type II:

It is also called senile osteoporosis, and it is related to bone mass lost due to the aging of cortical and trabecular bones.

 

Secondary osteoporosis:

Different diseases, medications, and lifestyle changes can cause osteoporosis.

 

There are some other factors that increase fracture risk and osteoporosis ¹⁰:

·       Age of the patient ¹¹

·       A low body mass index (BMI<21 kg/m2) is a significant risk factor for hip fracture ¹²

·       A history of a previous osteoporotic frac­ture is another important factor for further fracture risk and almost doubles the risk of spinal fractures 

·       Parental history of hip fracture ¹³

·       Smoking ¹⁴

·       Oral glucocorticoids ≥5 mg/d of predni­sone for >3 months (ever) ¹⁵

·       There is a dose-dependent relationship between alcohol intake and fracture risk. Daily intake 3 or more units of alcohol is associated with fracture   risk ¹⁶

·       Rheumatoid arthritis increases fracture risk independently of BMD, as well as the use of     glucocorticoids ¹⁷

 

Diagnosis of Osteoporosis:

Bone strength can be defined using BMD (70%) and bone quality (20%). It is easy to mea­sure BMD, but, in clinical settings, bone quality is not measurable yet. The diagnosis of osteo­porosis is established by the measurement of BMD or by the occurrence of a fragility frac­ture of the hip or vertebra or in the absence of major trauma (e.g., motor vehicle accident or fall from multiple stories). As defined by the World Health Organization (WHO), osteoporosis is present when BMD is 2.5 SD or more below the average value for young healthy women (a T-score of <-2.5 SD). A second, higher thresh­old describes “low bone mass” or osteopenia as a T-score that lies between -1 and -2.5 SD. “Severe” or “established” osteoporosis denotes osteoporosis that has been defined in the presence of one or more documented fragility fractures ¹⁸.

 

Bone mineral density can be easily measured to detect bone density, but the degree of de­terioration of the bone tissue cannot be mea­sured in clinical settings, except for the bio­chemical markers of bone tissue¹⁹. The International Society for Clinical Densitometry (ISCD) recommends using eth­nic- or race-adjusted Z-scores: Z-scores of −2.0 or lower are defined as “low bone mineral densi­ty for chronological age” or “below the expected range for age” and those above −2.0 are defined as “within the expected range for age”²⁰.  The United States Preventive Services Task Force (USPSTF) recommends the testing of all women aged 65 years and above and also for younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who exhib­its no additional risk factors ²¹. 

 

Fracture Risk Assessment Tool Model (FRAX):

The most important health consequence of osteoporosis is fractures. Recently, algorithms have been developed to predict the risk of frac­ture in individuals that incorporate significant predictors of fracture risk in addition to BMD. Estimating the 10-year risk of a major osteopo­rotic fracture (i.e., fracture of the hip, vertebra (clinical), forearm, or proximal humerus) is pos­sible with algorithms that integrate the weight of clinical risk fractures for fracture risk with or without information on the BMD have been developed (www.shef.ac.uk/ FRAX). They can be used to compute the 10-year probability of hip fracture or a major osteoporotic fracture (clinical spine, hip, forearm, or humerus). Clinical risk factors used in FRAX are as follows:

·       Current age

·       Sex

·       A prior osteoporotic fracture (including clinical and asymptomatic vertebral frac­tures)

·       BMD of femur neck

·       Low BMI (BMI<21 kg/m2)

·       Oral glucocorticoids ≥5 mg/d of predni­sone for >3 months (ever)

·       Rheumatoid arthritis

·       Parental history of hip fracture

·       Secondary causes of osteoporosis: Type-1 DM, early menopause <40 years, etc.

·       Being a past or current smoker

·       Alcohol intake (3 or more drinks/day)

 

Probabilities have been computed for several countries²².

 

A vertebral fracture is consistent with the diag­nosis of osteoporosis, even in the absence of a bone density diagnosis; it is an indication for pharmacologic treatment with osteoporosis

The diagnosis and clinical management of osteoporosis relies mainly on the measurement of bone density, because low bone density is associated with future risk of atraumatic and fragility fractures. During the last three decades several techniques have been developed for the measurement of bone density which are safe, precise, and accurate. Most of these techniques used some form of ionizing radiation (x-rays), and the measurement obtained is based on the attenuation of a beam of energy as it passes through bone and soft tissues. Although bone density shows a high correlation with bone strength, as much as 25-30% of the observed variation in bone strength may be due to the cumulative and synergistic effects of other factors, such as bone microstructure, architecture, and state of remodelling. In particular a measure of the biomechanical competence of the skeleton cannot be obtained using bone densitometer technique ^23.

 

The use of acoustic energy in the form of ultrasound wave has been suggested as possible choice for the assessment of bone integrity and to determine bone's response to mechanical loads to predict the risk of fracture²⁴. As a mechanical wave ultrasound may have the ability to provide information on several properties of bone since it interacts with bone in a fundamentally different way compared with ionizing electromagnetic radiation. This, combined with the fact that ultrasound involves no radiation and is relatively simple to implement and process, accounts for the widespread interest it has received recently. However, what distinguishes ultrasound from bone densitometry is the potential for sound to be modified by bone's structure, composition, and mass in such a way as to provide additional information about the tissue which can be related to the mechanical competence of the skeletal condition. Moreover, quantitative ultrasound will measure the density or content of bone mineral directly; it has frequently been described as a measure of bone quality ^25. There is a need to understand the relationship between the biomechanical properties of bone and the probability of a fracture risk using ultrasound. There are two basic approaches for ultrasonic interrogations of materials. The first uses a single transducer that acts as both transmitter and receiver. This is known as the 'reflection mode' and it is the method used to produce medical ultrasound images. In this mode, a portion of the ultrasound signal is reflected back to the transducer whenever a change in the acoustic properties of the media occurs. The reflection mode is simple to implement, as it requires only a single transducer.

 

The alternative approach for tissue analysis uses two transducers, one acting as transmitter and the other as a receiver of the ultrasound wave. This method is known as the 'transmission mode'. In this approach, the acoustic properties of the tissue can be obtained by comparing the received signal with a standard or reference waveform. The transmission mode requires two transducers, as well as access to both sides of the interrogated tissue. Transmission mode ultrasound has been used in assessment of bone strength and quality. The ability of an ultrasound wave to provide information about the medium or tissue through which it is being propagated depends on the way by which the wave is altered by the medium. Two principal types of alteration can occur: (i) the medium can alter the velocity of the wave, and (ii) the medium can reduce the amount of energy transmitted and thereby attenuate the wave.

 

Achilles Express bone ultrasonometer is used to evaluate bone status by measuring stiffness index in the heel (calcaneus bone) for the diagnosis and assessment of osteoporosis as shown in Figure 1. A typical ultrasonometer consist of high frequency ultrasound transmitter (Tx) and receiver (Rx), liquid crystal display (LCD), foot positioner, water filled membranes, calf support, strap and a toe peg. Measurements are performed with patient seated, with left foot placed on the foot positioner. The LCD consists of a menu for the measurement of patient data and display of results. Foot positioner keeps the patient's foot stationary during the measurement. The membranes are filled with water to provide coupling of the ultrasound signal from the transducer to the heel. Calf support aligns the heel with the transducer and the strap holds the leg and calf in the proper position. Toe peg helps the patient to keep the foot stationary and keep the heel aligned with transducers during measurement.

 

The choice of the calcaneus as a measurement site is validated by the fact that it contains 75 - 90% cancellous bone by volume ²⁶. Cancellous bone is eight times more metabolically active than cortical bone and age and disease related bone loss is more readily apparent at sites where there is a high percentage of cancellous bone. Moreover, calcaneus is highly stressed and weight-bearing bone and very active in remodelling process that shows changes within bone tissue earlier than compact bone. There is little soft tissue surrounding the calcaneus bone making it an excellent site for measurement and hence determination of a patients risk of fracture. The heel is surrounded by warm water encapsulated in inflated membranes, because water is the optimum medium for the transmission of ultrasound. A transducer on one side of the heel (Tx) converts an electrical signal into sound wave, which passes through water membranes and the patient's heel. A transducer at a fixed distance on the opposite side of the heel (Rx) receives the sound wave and converts it to an electrical signal that is analysed by the Achilles Express program. The instrument measures the speed of sound (SOS) and the frequency dependent broadband ultrasound attenuation (BUA), and combines them to form a clinical measure called stiffness index (SI). ²⁷

 

Speed of Sound (SOS):

Measurement of SOS in the heel involves accurate determination of the transit time (time of flight) of a sound wave as it passes through the heel. Transit time (Dt) is the elapsed time between the beginning of the transmitted wave pulse on one side of the heel and the beginning of the received wave pulse on the other side of the heel. The time is measured using high frequency, crystal controlled clock. SOS value is directly proportional to the bone mineral density.

 

Broadband Ultrasound Attenuation (BUA):

Measurement of BUA involves sending a broadband ultrasound pulse through the bone and measuring the reduction in intensity at different frequencies. Sending a voltage spike into the transducer generates a sound wave with a wide frequency spectrum ranging from 200-1000 kHz (abroad band pulse) with the strongest power signals centered at 500 kHz. This broadband frequency spectrum allows measurement of attenuation to occur over a range of frequencies. The bone acts as a low-pass filter allowing lower frequency sound to pass through with relatively little loss while transmission of higher frequencies is substantially impaired, or attenuated. Subtracting the values in this spectrum from a spectrum obtained by transmitting a sound wave through a weakly attenuating reference medium, such as water, provides the net attenuation at each frequency. A regression line is then drawn through the points on the net attenuation curve to obtain the attenuation slope (dB/MHz). Langton et al (1990) found that the preferential attenuation of the higher frequencies was greater in strong bone than it was in weak bone.

 

Stiffness Index (SI):

Stiffness Index which represents bone mineral density, combines BUA and SOS into a single clinical measure that has a lower precision error than either variable alone. This index is formulated by normalizing BUA and SOS through subtracting the lowest observable values (50 dB/ MHz and 1380 m/sec) from each and then scaling the resultant values. The stiffness index is the sum of the scaled and normalised BUA and SOS values. The resultant formula is empirically derived such that the index has 50% contribution due to SOS and 50% contribution from BUA.

 

SI = [(0.67 * BUA) + (0.28 * SOS) ] – 420

The SI is scaled in such a way to make the young adult value equal to 100. The normalized and scaled BUA and SOS values contribute about equally to the resulting stiffness index over the adult age range. Stiffness index results expressed as T-score and Z-score are used to assist physicians in the diagnosis of osteoporosis.

 

Fig. 1. Schematic of achilles express bone ultrasonometer

 

The T-score is the most significant parameter for the assessment of osteoporosis, which compares BMD of the subject with average BMD of young normal population. T-score above -1 is normal, between -1 to -2.5 is osteopenic (early stage of osteoporosis), and T-score lower than -2.5 is osteoporotic which is an indication of risk of fracture. Z-score compares BMD of the subject with average BMD of a population of the same age. This comparison determines whether the subject deviates from the normal pattern for his/her age and sex.²⁸

 

CONCLUSION: 

It is concluded that QUS can be effectively used to study the bone mineral loss and QUS clearly distinguishes between normal and osteoporotic subjects and can be a useful index in clinical management of osteoporosis. Risk factors help in the better assessment of bone mineral loss and osteoporosis. Thus Achilles Express ultrasonometer is a reasonable and accurate screening tool to detect low BMD.

 

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Accepted on 30.11.2019                                 © RJPT All right reserved

Research J. Pharm. and Tech 2020; 13(3):1592-1596.