Osteoporosis is a skeletal disorder characterized by weakened and fragile bones due to reduced bone mass, resulting from the loss of bone tissue.

Osteoporosis arises from an imbalance in the natural bone remodeling process, where bone breakdown (resorption) occurs faster than new bone formation. Key factors contributing to this imbalance include a decrease in estrogen levels and the effects of aging.

Classification of Osteoporosis

Based on its underlying cause, osteoporosis can be categorized as follows:

• Primary Osteoporosis: This type develops primarily due to aging or the bone-thinning effects associated with menopause in women. In primary osteoporosis, bone density naturally decreases as a person gets older. It’s important to note that this isn’t solely an inevitable part of aging but can also be due to insufficient peak bone mass achieved during younger years (childhood, adolescence, and early adulthood).

• Secondary Osteoporosis: This form results from a more significant loss of bone mass caused by other health conditions, such as being immobile for extended periods, as a side effect of certain medications (iatrogenic), due to hormonal imbalances (endocrine dysfunction), cancer, or chronic kidney disease.

Causes of Osteoporosis

Osteoporosis can be triggered by various factors that disrupt the delicate equilibrium between bone formation and breakdown.

Common contributors to osteoporosis include:

• Aging: The risk of osteoporosis increases with age. It’s thought that hormones like testosterone and estrogen play a crucial role in building and maintaining bone density, and their levels tend to decline with age.

• Menopause: The significant drop in estrogen levels during menopause accelerates bone loss in women.

• Nutritional Factors: Insufficient intake of calcium, low levels of vitamin D (essential for calcium absorption), a diet too high in phosphate relative to calcium, and inadequate overall calorie intake can all deprive the body of the necessary building blocks for bone remodeling.

• Chronic Renal Failure: Kidney disease can interfere with calcium and vitamin D metabolism, impacting bone health.

• Immobility: Lack of weight-bearing activity and movement reduces the signals needed for bone strengthening.

• Hyperparathyroidism: An overactive parathyroid gland leads to excessive parathyroid hormone production, which can draw calcium out of bones.

• Medications: Certain drugs, such as corticosteroids, anti-seizure medications, heparin (a blood thinner), and thyroid hormone (when taken in excess), can interfere with calcium absorption and how the body processes it.

• Chronic Glucocorticoid Abuse: Long-term use of high-dose glucocorticoids (a type of steroid medication) significantly increases the risk of osteoporosis.

Common risk factors

Factors that increase the likelihood of developing osteoporosis include:

• Age > 50: The risk of osteoporosis increases significantly after the age of 50.

• Menopause (lack of estrogen): The decrease in estrogen accelerates bone loss.

• Family history of fracture or osteoporosis: Genetics plays a role in bone density.

• History of at least two fractures: Experiencing multiple fractures can be an indicator of underlying bone weakness.

• Alcohol consumption: Excessive alcohol intake can negatively impact bone formation.

• Smoking: Nicotine and other chemicals in cigarette smoke inhibit the activity of osteoblasts, the cells that build bone.

• Insufficient physical activity (lack of bone remodeling): Weight-bearing exercise stimulates bone formation and remodeling.

• Glucocorticoids (steroid-induced osteoporosis): These medications can significantly weaken bones.

• Proton pump inhibitors: Long-term use of these medications (used to reduce stomach acid) has been linked to an increased risk of fractures, possibly due to impaired calcium absorption.

Pathophysiology of Osteoporosis

The normal process of bone maintenance involves a balance between two key types of cells: osteoblasts, which build new bone, and osteoclasts, which break down old bone.

Bone resorption, the breakdown of bone tissue, is carried out by osteoclasts. Following this process, osteoblasts then deposit new bone material.

The balance between the activity of osteoblasts and osteoclasts within a bone is influenced by various factors, including immune cells (macrophages) and the body’s innate and adaptive immune responses. This balanced activity leads to the formation of healthy bone.

In osteoporosis, this delicate balance is disrupted. There is an increase in the activity of osteoclasts relative to the activity of osteoblasts. This imbalance results in excessive bone breakdown (resorption) and ultimately leads to a loss of bone mass.

Reduced total bone mass: In osteoporosis, the normal, continuous process of bone turnover is altered. The rate at which osteoclasts break down bone becomes greater than the rate at which osteoblasts create new bone, leading to an overall reduction in the total amount of bone.

Progression: As osteoporosis progresses, the internal structure of the bones changes. They become more porous, meaning they develop more holes and spaces, making them brittle and fragile. As a result, the bones become more susceptible to fractures, even under stresses that would not normally break a healthy bone.

The overall consequence of these changes is a net loss of bone mass over time, weakening the skeleton.

Role of Hormones

Besides estrogen, calcium is essential for maintaining healthy bone turnover.

A deficiency in both calcium and vitamin D impairs the process of building new bone (bone deposition). Vitamin D is crucial for the body’s ability to absorb calcium from the gut.

When calcium levels in the blood are low, the parathyroid glands release parathyroid hormone (PTH). PTH acts to increase bone resorption, releasing calcium from the bones into the bloodstream in an attempt to restore adequate calcium levels.

The role of calcitonin, a hormone produced by the thyroid gland, is less clear and likely less significant in osteoporosis. Calcitonin’s primary action is to promote bone deposition.

Clinical Features of Osteoporosis

• Fractures: Often, the first noticeable sign of osteoporosis is a fracture. These fractures commonly occur as compression fractures in the vertebrae (bones of the spine).

• Kyphosis: The gradual collapse of vertebrae can occur without any noticeable symptoms initially. This progressive curvature of the spine is known as kyphosis, sometimes referred to as a “dowager’s hump,” and is associated with a loss of height.

• Decreased calcitonin: The level of calcitonin, a hormone that inhibits bone breakdown and encourages bone formation, is often reduced in individuals with osteoporosis.

• Decreased estrogen: Estrogen, which plays a role in slowing down bone breakdown, decreases with age, particularly after menopause in women.

• Increased parathyroid hormone: Parathyroid hormone levels tend to increase with aging, which can contribute to increased bone turnover and resorption.

Diagnosis / Investigations

The most common and widely used test to measure bone mineral density is:

• Dual-energy X-ray Absorptiometry (DXA): This is a fast, painless, and non-invasive procedure. During a DXA scan, you lie on a cushioned table while a scanner passes over your body, using low levels of X-rays. The test measures the bone mineral density (BMD) of your skeleton, particularly at sites that are prone to fracture, such as the hip and spine. Measuring bone density using DXA at the hip and spine is generally considered the most reliable method for diagnosing osteoporosis.

Management of Osteoporosis

Aims

• To prevent further loss of bone density.

• To lower the risk of bone fractures.

• To increase bone mass density and thereby reduce the risk of fractures.

Medical Management

• Exercise: Physical activity, especially weight-bearing exercise, helps to stimulate bone mineralization and the deposition of new bone tissue, particularly during growth periods. High-impact exercises have been shown to be effective in preventing osteoporosis. However, it’s important to note that high-impact exercise may not be suitable for individuals with certain conditions, such as poor nutrition related to anorexia nervosa or celiac disease.

• Physical activity: Various forms of exercise, including aerobics, weight lifting, and resistance training, have been shown in multiple studies to help maintain or even increase bone mineral density (BMD) in postmenopausal women.

• Nutrition: Consuming a diet rich in calcium and vitamin D is crucial for preventing bone loss. Individuals at higher risk of osteoporosis, such as those on long-term steroid medication, are often prescribed vitamin D and calcium supplements.

• Diet: Adequate protein intake is essential for maintaining the health and function of the musculoskeletal system and can help reduce complications that may arise after an osteoporotic fracture.

• Smoking cessation: Quitting smoking can help prevent osteoporosis. The use of tobacco products has a detrimental effect on the skeleton and overall health.

• Avoiding excessive alcohol intake, or drinking only in moderation: Excessive alcohol consumption can interfere with bone health.

• Medications: When possible, using the lowest effective doses of certain medications known to be associated with osteoporosis, such as anticonvulsants or corticosteroids, is recommended.

• Fall prevention: Taking steps to reduce the risk of falls is crucial in preventing fractures. Strategies include:

  • Installing assistive devices in bathrooms to aid with hygiene and using hip protectors.

  • Removing obstacles from walking paths to prevent tripping hazards.

  • Ensuring proper correction of visual impairments to improve mobility and reduce the risk of falls.

  • Addressing slippery conditions by using cotton rugs and keeping the environment dry.

Pharmacological Management

• Calcium supplements with vitamin D: To ensure sufficient calcium intake, a calcium supplement, often combined with vitamin D, may be prescribed. It’s usually recommended to take these supplements with meals or a beverage high in vitamin C to enhance absorption. However, calcium supplements should not be taken at the same time as bisphosphonates. Recommended daily intake: Dietary calcium 1200 mg (with supplemental calcium limited to ≤ 500 mg if dietary intake is insufficient) and Vitamin D 800–2000 IU/day.

• Bisphosphonates: These are typically the first-line medication for treating osteoporosis. They are available in oral forms such as:

  1. Alendronate (70mg taken orally once weekly).

  2. Risedronate (35mg taken orally once weekly or 150mg taken orally once monthly).

  3. Ibandronate (150mg taken orally once monthly, or 3mg administered intravenously (IV) every 3 months).
     Alternatively, zoledronic acid can be given as a yearly intravenous infusion (5mg annually via IV). Bisphosphonates work by increasing bone mass and reducing bone loss through inhibiting the function of osteoclasts.

• Calcitonin: This medication directly inhibits osteoclasts, thereby reducing bone loss and increasing bone mineral density. It is often used for postmenopausal women with osteoporosis. The typical dosage is 100 units administered subcutaneously daily or 200 units administered intranasally daily.

• Selective estrogen receptor modulators (SERMs): SERMs, such as raloxifene, are considered a second-line treatment option. They help reduce the risk of osteoporosis by maintaining bone mineral density without having the same estrogenic effects on the uterus as estrogen itself. The standard dosage is 60mg taken orally once daily.

• Parathyroid hormone: Medications like Teriparatide (20mcg administered subcutaneously daily) and Abaloparatide (80mcg administered subcutaneously daily) are recombinant forms of parathyroid hormone. They stimulate osteoblasts to build new bone matrix and improve overall calcium absorption.

Surgical Management

Surgery is not typically the initial treatment for osteoporosis. Procedures like vertebroplasty, kyphoplasty, lordoplasty, and vesselplasty are generally reserved for patients who have vertebral fractures due to either pathological conditions or osteoporosis.