Introduction

Overview of metabolic bone disorders

Metabolic bone disorders are endocrine disorders that have been reported to impact over 200 million people globally, and they're the third most prevalent human diseases after thyroid and diabetes.¹ In recent years, there has been a drastic increase in the prevalence rate of metabolic bone disorders due to the deficiency of body intake of calcium, phosphorus, and vitamin D.² 

The term 'metabolic bone disorder’ refers to a group of disorders with a marked progressive loss of bone strength and density.⁶ These result in the changes in bone production, resorption, and mineralisation. Hormonal imbalances, poor diet, and other factors might result in metabolic bone disorder.⁷ Some of the most commonly occurring metabolic bone disorders include osteoporosis, osteomalacia, hyperparathyroidism, etc. These conditions result in the child's bone growth, frequent fractures, and loss of bone.³ And they primarily affect old women, more followed by the older men.⁴ 

Studies have shown that vitamin D insufficiency affects fetal bone health.⁵ Early diagnosis might prove useful to reverse the damage along with lifestyle modifications. A healthy, well-balanced diet enriched with vitamin D, calcium, and phosphorus, together with exercise, is necessary for bone health.⁴ The main risk factors associated with metabolic bone disorders include early vitamin D insufficiency, deficiency of minerals such as calcium and phosphorus, premature birth, etc.⁸

Risk factors for metabolic bone disorders

Major risk factors that result in metabolic bone diseases are:

1. Non-modifiable factors

The main non-modifiable factors include age, gender, and genetics. 

• After the age of 50, the human body becomes more vulnerable to fractures, and the chances of osteoporosis increase, particularly in females who undergo menopause. Therefore, women are at more risk than men⁴ 
• Many metabolic bone diseases have genetic origins. These disorders can be classified as somatic single gene defects, germline single gene abnormalities, or involve multiple genetic variants⁹
• Defects due to maternal or gestational factors: If the mother was a chronic smoker and smoked during the time of pregnancy, it can be a primary reason for the development of low bone density. Also, if the mother, during the late stages of pregnancy, has performed intense exercise, it could contribute towards metabolic bone disease¹⁰
• Malnutrition or hypocalcemia in the mother could also play a role in the disease's development¹⁰
• Other conditions like chronic liver disease, chronic renal damage, and congenital abnormalities in vitamin D production¹⁰

2. Modifiable factors
   • Insufficiency of vitamin D intake: Studies have shown that low vitamin D intake can result in bone demineralisation, which in turn affects the body's absorption of calcium.¹¹ To compensate for this, calcium is released from the bones; this alters the bone architecture and raises the risk of fractures. Bone mineral density and fracture risk are directly correlated¹¹ 
   • Insufficient intake of phosphorus, calcium, and magnesium: Rickets is a type of metabolic disorder that occurs due to a deficiency of calcium, phosphorus, and vitamin D¹²   
   • Drugs like anticonvulsants, anticoagulants, diuretics, calcium antagonists, etc., are reported to reduce bone density and result in bone abnormalities¹⁰
   • Prolonged immobilisation and physical inactivity have been reported to be clinical risk factors for fragility fracture¹³
   • Excessive consumption of alcohol and chronic smoking may degrade bone density and exacerbate osteoporosis³

Metabolic bone disease 

• Osteoporosis: This is a bone disorder that occurs due to low bone density. It decreases the bone strength and raises the risk of fractures. Additionally, it compromises bone mineralisation and affects the mineral density of the bone. Initially, it is asymptomatic, and it is mostly hard to get diagnosed until any fracture occurs in the body¹⁴
• Rickets: This is a condition caused by a defect in the mineralisation of the epiphyseal plates in the bone. Rickets can either be acquired or inherited. The most common cause is vitamin D deficiency, and there are a wide range of presentations, including irritability, growth retardation, and sudden death. Rickets need to be treated early to avoid long-term consequences¹⁵   
• Disorders related to the parathyroid: Bone diseases can result from the parathyroid gland hormone, which is responsible for controlling blood levels of calcium and phosphorus³ 

Nutritional prevention strategies

1. Adequate intake of calcium is essential as it is required for the lifetime deposition of bone minerals. More than 99% of calcium in the body is stored in teeth and bones. A certain amount is present in the plasma and extracellular fluid, and it helps in determining the bone resorption levels¹⁸
   • Dairy products like cheese, milk, etc and green leafy vegetables such as okra and kale have high calcium content ¹⁹
2. Vitamin D is essential for calcium and phosphorus homeostasis and bone metabolism. With chronic deficiency of vitamin D, hypocalcemia might result, which in turn might cause secondary hypothyroidism. Secondary hypothyroidism leads to bone demineralisation faster than the usual pace and might result in metabolic bone diseases like osteomalacia, rickets, etc. Therefore, it is always advisable to intake sufficient quantities of vitamin D¹⁶
   • Sources of vitamin D: Numerous breakfast cereals, as well as wide varieties of yogurt, orange juice, and margarine, have vitamin D. Fish liver oil and fatty fish such as salmon, tuna, and mackeral, etc are the natural sources of vitamin D. Other sources of vitamin D include cheese, egg yolks, beef liver, and mushrooms, which have a meager amount of vitamin D.¹⁷ Also, sunlight helps the body to manufacture vitamin D in the body
   • Adults who are under 65 should take 600-800 IU of vitamin D3, and people who are over 65 should take at least 800-1000 IU of vitamin D3 to prevent vitamin D deficiency and related consequences¹⁶
3. Along with calcium and vitamin D, other nutrients like proteins and minerals like phosphorous, magnesium, zinc, etc. Vitamin K and C, along with omega-3 fatty acids, improve bone strength²⁰

Lifestyle prevention strategies

• Along with a healthy diet, it is always beneficial if appropriate exercises are done to keep the bones healthy. Weight-bearing exercises like walking, dancing, hiking, and running focus on supporting the body's weight against gravity. Apart from this, resistance training exercises help strengthen bones²¹
• Prevention of fall: Fall is the biggest risk, and this should be prevented to safeguard the bones²²
• Smoking has adverse effects on bone health; it results in bone resorption and inhibits bone formation. Nicotine has been reported to lower estrogen levels, lowering bone mass, and it has also been demonstrated that smoking increases free radicals in the body²³ 
• Alcohol has been reported to present a high incidence of fractures due to osteoporosis.

Medical prevention strategies

• Early diagnosis is always beneficial and equally crucial to prevent long-term complications. Firstly, risk factor assessment should be done, and based on that, bone mineral density (BMD) testing should be done. Diagnosis is usually done by radiographic analysis followed by the biomarker analysis in the blood. The common biomarkers are alkaline phosphatases, osteocalcin, acid phosphatases, hydroxyproline, etc
• Primarily, there are two different kinds of medication therapies for osteoporosis. First, antiresorptive agents are the drugs that slow down bone loss. Second, anabolic agents are the agents that usually promote bone growth
  • Antiresorptive drugs are the agents that contain bisphosphonates, estrogen, calcitonin, and selective estrogen receptor modulators (SERMs). These agents lessen bone turnover by reducing the activity of the osteoclasts, resulting in a decrease in the overall bone loss. They raise the bone mineral density by causing the new bone to grow in the gaps of resorption. FDA-approved bisphosphonates are alendronate and risedronate
  • The patients who could not get effective relief using antiresorptive therapy should go for anabolic drug therapy. The FDA-approved anabolic agent is teriparatide, which is the synthetic version of the parathyroid hormone

Prevention in specific populations

• Children and adolescents
  • The skeleton expands both in size and density over the first 2 decades of life, where the teens account for maximum accumulation of more than half of their peak bone mass. The rate of bone tissue loss exceeds the bone building. Thus, optimising peak bone mass at the crucial stages of growth is essential for maintaining good bone health. Therefore, it is essential to take an adequate amount of vitamin D and calcium, etc., the required nutrients for maintaining healthy bones²⁴
• Postmenopausal women
  • Estrogen helps in maintaining healthy bones, but later, when the estrogen level declines due to menopause, there is accelerated bone loss, which results in an increased risk of osteoporosis
• Older adults
  • Older adults are always at risk of fractures due to the extreme decline in bone mass. They should always be assisted in performing daily activities as they might be prone to falls.

Conclusion

Metabolic bone disorder is a group of disorders with a marked progressive loss of bone strength and density.⁶ These result in the changes in bone production, resorption, and mineralisation. Some of the most commonly occurring metabolic bone disorders include osteoporosis, osteomalacia, hyperparathyroidism, etc. Early diagnosis might prove useful to reverse the damage, along with lifestyle modifications. A healthy, well-balanced diet enriched with vitamin D, calcium, and phosphorus, together with exercise, is necessary for bone health.⁴ The major risk factors are age, gender, and genetics, which are non-modifiable. Vitamin D, phosphorus, and other mineral deficiencies are modifiable risk factors. Prevention can be based on the following strategies: nutritional prevention, lifestyle modification, medical prevention, and fall prevention. By adopting these strategies, patients can lower their chances of developing metabolic bone disorders, ultimately enhancing their quality of life.