Osteoporosis – Weakening of the Bones

A 42-year-old patient of mine said, “I never smoked, my drinking is limited, and overall I am healthy,” referring to some of the risk factors for the disease. However, from age 24, she experienced problems with dairy products and could not consume them. She was at risk because of the low-calcium diet and her family history of osteoporosis. She even mentioned that people around her are surprised that she has osteoporosis, “everyone thinks it is a little old lady’s disease.”  She knows the importance of talking about osteoporosis with people and believes how a good fitness program can help rebuild bones and so, she exercises regularly. “These are the cards you are dealt,” she added, which shows her positive attitude. “I feel lucky to live in this day and that there are medicines to help improve osteoporosis. Ten years ago, they did not have some of these medicines.”

The lack of awareness, however, still lingers around our fellow companions. Through this article, we would like to shed some light on the present scenario of osteoporosis.

Definition: It is the most common metabolic bone disease in the United States. Often overlooked and undertreated because it is often clinically silent and results in symptoms only when there is a fracture. Osteoporosis can result in devastating psychosocial, physical, and economic consequences. Fractures cause morbidity and mortality (>20% 1 year for hip fractures)

By history: Fragility fracture: hip/vertebral fractures,Dowges hump

BY DEXA (WHO)

World Health Organization (WHO) criteria define a normal T-score value as within one standard deviation (SD) of the mean BMD value in a healthy young adult.

Normal bone density:  -1 ≤ T score; Osteopenia: -2.5 < T score < -1; Osteoporosis: T score ≤ -2.5;

Severe osteoporosis: T score ≤ -2.5 plus fragility fracture

Fragility fracture: Low trauma fracture that should not have caused a fracture in a younger person (standing height falls).Slipping down two stairs is a fragility fracture, but a flight of stairs is not. The most commonly involved sites are the hip, spine, and wrist.

COMPOSITION OF BONE-

• 35% organic matrix: 90% collagen, 10% other proteins
• 65% inorganic elements: Hydroxyapatite: Ca10(PO4)6(OH)2, 99% of our calcium and 85% of our phosphorus
• Cells: Osteocytes, Osteoblasts, Osteoclasts

Precise interplay between all three components is necessary for the bone to mineralize

Type 1 collagen fiber maturation: Because Type I collagen is the most abundant protein found in bone, defects in Type I collagen can result in alterations of material property, ultimately leading to fragility fractures.

BONE MASS ACQUISITION OVER A LIFETIME

 

Diagnosis: 1. Previous fragility fracture (fall from standing height), 2. Low bone density by DXA (T score below -2.5) [Bone density scanning, also called dual-energy x-ray absorptiometry (DXA) or bone densitometry, is an enhanced form of x-ray technology that is used to measure bone loss. DXA is today’s established standard for measuring bone mineral density (BMD).] 3. Increased fracture risk based on FRAX. [FRAX score estimates the probability of a fracture within the next 10 years. The output is a percentage, and higher values indicate a greater risk of fracture. The score refers to fractures in the: hip.] https://wiki.galenhealthcare.com/images/6/66/FRAX_2019.png.

Risk factors: Smoker, Alcohol >3 drinks per day, Low body weight( <58kg), Female, Older age, 1^st degree relative with hip fracture, Nulliparity, Prednisolone>5mg for three months, Known malabsorption/malnutrition, Premature menopause (<45), Chronic Stress ( Itactivates the HPA axis and sympathetic nervous system, suppresses the secretion of gonadal hormone and growth hormone, and increases inflammatory cytokines, eventually leading to bone loss by inhibiting bone formation and stimulating bone resorption).

MOST COMMON SECONDARY CAUSES OF OSTEOPOROSIS –

 

Diseases	Metabolic Conditions or nutritional Deficiencies	Drugs	Disorders of collagen metabolism	Others
Hyperthyroidism	Alcoholism	Steroids	Osteogenesis imperfecta	Renal tubular acidosis
Hyperparathyroidism	Hypercalciuria	Antiepileptics	Homocystinuria	Organ transplantation
Myeloma	Vitamin D deficiency	GnRH agonists	Ehler danlos syndrome	Gauchers
Rheumatoid arthritis	Weight loss	Depo-Provera	Marfans syndrome	Thalassemia
COPD	Gastric surgery	Aromatase inhibitors		Mastocytosis
Hypogonadism	Anorexia Nervosa	Excess thyroxine		Immobilization
Type 1 Diabetes mellitus	Malabsorption	Heparin
Growth hormone deficiency	Malnutrition	PPIs
Acromegaly	Prolonged TPN	TZD’s
Inflammatory bowel disease	Calcium deficiency
Cushing’s	Chronic Liver disease

Natural History, Complications, and Prognosis

Most of the patients with osteoporosis, if left untreated, develop fractures. Osteoporotic fractures are also associated with deep venous thrombosis, kyphosis, and reduced quality of life due to immobility and an increase in mortality. With the appropriate and timely usage of medications, calcium, and vitamin D supplementation, the prognosis is usually good.

Diagnosis

Signs and symptoms: Osteoporosis is usually asymptomatic until one experiences an osteoporotic fracture. The hallmark symptom of which is bone pain, and the significant signs that appear gradually include immobility, bedsores, decrease in height, and stooped posture.

Physical examination :Osteoporosis is generally asymptomatic until the bone mass loss leads to a fracture. Fractures can be divided into acute(involving femoral neck) and chronic ones(involving vertebral bones).The characteristic feature of femoral fracture is immobilization, and the main feature of vertebral fracture is Dowager’s hump appearance. Any other secondary causes of the disease (e.g., chronic corticosteroid use or hyperthyroidism) may have their symptoms, signifying a risk factor for osteoporosis.

On physical examination, patients with vertebral compression fractures may demonstrate the following:

• With acute vertebral fractures, point tenderness over the involved vertebra
• Thoracic kyphosis with an exaggerated cervical lordosis (dowager’s hump)
• The subsequent loss of lumbar lordosis
• A decrease in the height of 2-3 cm after each vertebral compression fracture and progressive kyphosis

Patients with hip fractures may demonstrate the following:

• Limited ROM with end-range pain on a FABER (flexion, abduction, and external rotation) hip joint test
• Decreased weight-bearing on the fractured side or an antalgic gait pattern

Patients with Colles fractures may have the following:

• Pain on movement of the wrist
• Dinner fork (bayonet) deformity

Patients with pubic and sacral fractures may have the following:

• Marked pain with ambulation
• Tenderness to palpation, percussion, or both
• With sacral fractures, pain with physical examination techniques used to assess the sacroiliac joint (e.g., FABER, Gaenslen, or squish test)

Balance difficulties may be evident, especially in patients with an altered center of gravity from severe kyphosis. Patients may also have trouble performing tandem gait and performing single-limb stance.

Laboratory findings: Lab tests have a limited role in the diagnosis. However, they may be used for differentiating primary versus secondary causes. Baseline tests for the diagnosis of osteoporosis include complete blood count (CBC), serum calcium, phosphate, alkaline phosphatase(ALP), and 25-(OH)-vitamin D. The tests for diagnosing secondary osteoporosis include 24 hr serum calcium, serum protein electrophoresis, and serum thyroid hormones.

X-ray: It may help diagnose osteoporosis. The suggestive finding of osteoporosis is bone mass loss on X-ray. Primarily, the loss is mainly in the bony trabecula, as compared to the cortex. The most commonly monitored bones for osteoporosis are the femoral neck, lumbar vertebrae, and calcaneus. Since Plain radiography needs at least 30-50% of the bone loss to demonstrate decreased bone density, it is not a very sensitive modality.

CT scan: Findings suggestive of osteoporosis on a bone CT include decreased bone mineral density (BMD).To describe the bone strength more precisely, it seems necessary to do quantitative assays such as dual-energy X-ray absorptiometry (DXA) and CT scan (especially volumetric quantitative CT (vQCT)). Modalities for assessing osteoporotic fracture risk, without any destruction or invasion, include high-resolution CT (hrCT) and micro CT (μCT). The only tests that are possible in vivo are hrCT and vQCT.

MRI: The magnetic resonance imaging (MRI) technique is very precise in measuring trabecular bone structure, and it could be a suitable surrogate for multiple sites bone biopsy. As DXA can measure both trabecular and cortical simultaneously, MRI would be a better choice to only assess the trabecular bone part. The most impressing aspect of MRI in diagnosing osteoporosis is the ability to take in vivo images of trabecular bones. The plain resolution starts at about 150 μm and slice thickness starts at 300 μm, precisely measuring trabecular bones.

Echocardiography/Ultrasound: There are no echocardiography findings associated with osteoporosis. Quantitative ultrasound may be helpful in the diagnosis of osteoporosis. Ultrasound findings diagnostic of osteoporosis include bone mass loss, mainly trabecular bone that is the major bone type affected in osteoporosis. Problems with the DXA method have led physicians to choose some methods with fewer side-effects and limitations, such as ultrasound (mainly quantitative), which could diagnose osteoporosis with lower radiation, lower price, and higher availability. The most common site of ultrasound application is peripheral parts, such as calcaneus and phalanges.

Other imaging findings: The most important modality for measuring bone mineral density (BMD), on which every osteoporosis diagnostic and therapeutic decision is based, is dual-energy X-ray absorptiometry (DEXA). DEXA is a 2-dimensional image of a 3-dimensional subject, mainly depends on the size of the bone studied. DEXA is the gold standard for the diagnosis of osteoporosis and fracture risk assessment. Finite element modeling (FEM) is an engineering computer-based simulation software that typically simulates the physical loading effects on materials. The effects may be strain or compression, while the subject is determined as net-like elements connected to each other. BMD is focused on density and does not imply for microstructure or architecture of bones. One of the most potent methods to determine the microstructure is the trabecular bone score (TBS) as a complementary method for DEXA.

WHO SHOULD HAVE A BONE MINERAL DENSITY SCREENING?

Guidelines from the American Association of Clinical Endocrinologists/American College of Endocrinology include the following recommendations for choosing drugs to treat postmenopausal osteoporosis:

• First-line agents for most high fracture risk patients: alendronate, risedronate, zoledronic acid, ibandronate, raloxifene (latter two not recommended for the reduction of nonvertebral or hip fracture risk)
• First-line agents for spine-specific indications in select patients: ibandronate and raloxifene
• First-line agents for high fracture risk patients unable to use oral therapy: zoledronic acid, denosumab
• First-line agents for very high fracture risk, including those with multiple fractures: teriparatide, abaloparatide for up to two years, romosozumab for up to one year (should not be considered in women at high risk of cardiovascular disease or stroke)
• Sequential agents: anabolic agents (e.g., abaloparatide, teriparatide, romosozumab) should be followed with a bisphosphonate or denosumab

Guidelines from the American College of Rheumatology for the treatment of glucocorticoid-induced osteoporosis include the following:

• Designation of moderate-to-high risk or low-risk categories for adults ≥40 years of age receiving long term glucocorticoids by fracture risk score (using the FRAX score)
• No tools to estimate absolute fracture risk in children or adults ≤40 years of age. Considered high risk if previously sustained osteoporotic fracture and moderate risk if on glucocorticoid treatment ≥7.5 mg for 6 months and had either hip or spine BMD Z-score less than -3 or 2 or rapidly declining hip or spine BMD ≥ 10% in one year while on glucocorticoid treatment
• Strong or conditional recommendations for initiation of treatment in women with non-childbearing potential and men on glucocorticoids with high, moderate, to low fracture risk in order of preference: oral bisphosphonates, IV bisphosphonates, teriparatide, denosumab, and raloxifene

Treatment

Medical therapy

Lifestyle modification: Various lifestyle modifications that can be implemented to prevent the development/ progression and treat osteoporosis include diet, exercise, smoking cessation, alcohol consumption, Calcium, Vitamin D supplementation, and fall prevention. The patient should consume 1200 to 1500 mg of calcium daily, by dietary means (e.g., 8 oz glass of milk contains approximately 300 mg of calcium) or via supplementation. New vitamin D intake recommendations are 400-800 IU daily in adults up to age 50 and 800 – 1,000 IU daily in those over 50. Multiple studies have shown that aerobics, weight lifting, and resistance exercises can all maintain or increase BMD in postmenopausal women. In addition to maintaining adequate vitamin D levels and physical activity, as described above, several strategies have been demonstrated to reduce falls.

Pharmacotherapy: The mainstay of treatment in primary osteoporosis is based on lifestyle modifications. Most of the time, in high-risk patients and people with a history of osteoporotic fracture, medical therapy is necessary. Bisphosphonates are the first-line treatment for osteoporosis. Raloxifene is the second-line treatment of osteoporosis in postmenopausal women for both treatment and prevention. Denosumab is a human monoclonal antibody designed to inhibit RANKL (RANK ligand), a protein that acts as the primary signal for bone removal. It is used to treat osteoporosis in older men and postmenopausal women. Teriparatide and Abaloparatide are human recombinant parathyroid hormones used to treat postmenopausal osteoporosis in women with a high risk of fracture or increase bone mass in men with osteoporosis.

Surgery: Surgery is not the first-line treatment option for patients with osteoporosis. Vertebroplasty, kyphoplasty, lordoplasty, and vesselplasty are usually reserved for patients with either pathological or osteoporotic vertebral fractures in patients, refractory to medical therapy. Surgery options for osteoporosis are minimal. In the case of hip fracture, open reduction internal fixation, or total hip replacement surgery are the options.

Primary Prevention: In osteoporosis, some lifestyle modification strategies would be beneficial for both primary prevention and initial treatment; osteoporosis majorly depends on lifestyle in every stage of the disease. Lifestyle modification and calcium supplementation are the best early and long-term measures for the prevention of osteoporosis. There are also medications available that can be used to prevent the worsening of osteoporosis. The primary prevention of osteoporosis is essential because the micro-architectural changes that occur in osteoporosis are mainly irreversible.

Secondary Prevention: Effective measures for the secondary prevention of osteoporosis include pharmacological therapy and also lifestyle modification as soon as osteoporosis is diagnosed.

Future or Investigational Therapies: Some future antiresorptive drugs that are not yet improved by US food and drug administration (FDA) include calcitriol, genistein, other bisphosphonates (etidronate, pamidronate, and tiludronate), PTH (1-84), sodium fluoride, strontium ranelate, and also tibolone.

Acknowledgements-

1. WikiDoc-Dr. Michael Gibson
2. Norman Regional Health Centre- Dr. Lubna Mirza
3. Armed Forces Medical College,Pune,India