Metabolic Bone Disorders

Osteoporosis refers to a decrease in bone mass and density, microarchitectural disruption, and increased skeletal fragility, leading to a reduction in the strength of bone that leads to an increased risk of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal, or senile, and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis most often presents clinically with fractures (most commonly, vertebral fractures) and loss of vertebral height. Diagnosis is established by measuring bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA). Management includes lifestyle modifications, maintaining adequate levels of calcium and vitamin D, and administration of pharmacologic agents (of which bisphosphonates are considered the 1st-line therapy).

Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Calcium levels are regulated and affected by factors such as dietary intake and pH, and the levels of parathyroid hormone (PTH), vitamin D, and albumin. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Generally, neuropsychiatric (confusion, altered mental status), GI (vomiting, abdominal pain), musculoskeletal (bone pain, weakness), and renal (polyuria, polydipsia) manifestations are seen. Confirmation of hypercalcemia is required. Correction of the value is based on the albumin levels or after determining the ionized calcium levels (the metabolically active form), which is followed by determining PTH levels. Subsequent laboratory tests and imaging studies are ordered based on history and presentation. Correction of hypercalcemia depends on its severity. Calcium levels > 14 mg/dL are treated using IV isotonic saline hydration, calcitonin, and bisphosphonates. Hemodialysis is considered in rare cases. Treatment of the underlying cause is recommended.

Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Patients can exhibit symptoms from neuromuscular irritability (tetany, Chvostek sign, Trousseau sign) to cardiovascular dysfunction (arrhythmia). Confirmation of hypocalcemia is required with correction of the value depending on albumin level or ionized calcium (the metabolically active form), followed by PTH level, and determination of the underlying cause. Correction of calcium is dictated by the degree of severity of hypocalcemia. In severe cases, IV calcium administration is required. Treatment of the underlying cause is recommended.

Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Deficiency of PTH results in hypocalcemia, which leads to increased neuromuscular excitability and osteosclerosis, as well as cardiac and neuropsychiatric manifestations. Treatment is based on calcium and vitamin D supplementation.

Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary, or tertiary. Primary hyperparathyroidism is an inherent disease of parathyroid glands associated with abnormal secretion of PTH. Secondary hyperparathyroidism results from abnormalities of calcium metabolism, which, if left untreated, can progress to tertiary hyperparathyroidism, which is associated with hypertrophy of the parathyroid gland and oversecretion of PTH even if the primary cause is eliminated. Most individuals are asymptomatic, though late-stage, symptomatic disease may present with kidney stones, bone fractures, abdominal pain, and change in mental status. Diagnosis is based on biochemical parameters, which include serum PTH, calcium, and phosphate levels as well as urinary calcium. Management relies mostly on surgical parathyroidectomy for primary and tertiary hyperparathyroidism. Management of secondary hyperparathyroidism is focused on treatment of the underlying disease.

Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Primary hyperparathyroidism is an inherent disease of parathyroid glands associated with abnormal secretion of PTH. Secondary hyperparathyroidism results from abnormalities of calcium metabolism, which, if left untreated, can progress to tertiary hyperparathyroidism, which is associated with hypertrophy of the parathyroid gland and oversecretion of PTH even if the primary cause is eliminated. Diagnosis is based on biochemical parameters, which include serum PTH, calcium, and phosphate levels as well as urinary calcium. Management relies mostly on surgical parathyroidectomy for primary and tertiary hyperparathyroidism. Management of secondary hyperparathyroidism is focused on treatment of the underlying disease.

Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Calcium levels are regulated and affected by factors such as dietary intake and pH, and the levels of parathyroid hormone (PTH), vitamin D, and albumin. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Generally, neuropsychiatric (confusion, altered mental status), GI (vomiting, abdominal pain), musculoskeletal (bone pain, weakness), and renal (polyuria, polydipsia) manifestations are seen. Confirmation of hypercalcemia is required. Correction of the value is based on the albumin levels or after determining the ionized calcium levels (the metabolically active form), which is followed by determining PTH levels. Subsequent laboratory tests and imaging studies are ordered based on history and presentation. Correction of hypercalcemia depends on its severity. Calcium levels > 14 mg/dL are treated using IV isotonic saline hydration, calcitonin, and bisphosphonates. Hemodialysis is considered in rare cases. Treatment of the underlying cause is recommended.

Multiple endocrine neoplasia syndromes are autosomal dominant inherited conditions characterized by 2 or more hormone-producing tumors involving the endocrine organs. There are different types of MEN, namely MEN1–4. The MEN1 syndrome is associated with MEN1 gene mutation and has a predilection for primary hyperparathyroidism, pituitary adenomas, and pancreatic tumors (the 3 P’s). Due to the RET proto-oncogene mutation, MEN2 syndrome can be further categorized as MEN2A and MEN2B. Medullary thyroid carcinoma and pheochromocytoma are common features. The MEN2A variant is associated with primary hyperparathyroidism, whereas MEN2B (also considered MEN3) is associated with neuromas and Marfanoid habitus. The newer and rare entity, MEN4, has features of MEN1 but results from CDKN1B mutations. The diagnosis is clinical, and tumors are detected based on imaging and correlating hormone levels. Genetic testing plays a crucial role in MEN2 syndromes in determining further management. Treatment is dependent on the tumors that are present and genetic mutation.

Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Deficiency of PTH results in hypocalcemia, which leads to increased neuromuscular excitability and osteosclerosis, as well as cardiac and neuropsychiatric manifestations. Treatment is based on calcium and vitamin D supplementation.

Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis most often presents clinically with frequent fractures and loss of vertebral height. Diagnosis is established by measuring bone mineral density. Management includes lifestyle modifications, maintaining adequate levels of calcium and vitamin D, and the use of bisphosphonates.

Rickets and osteomalacia are disorders of decreased bone mineralization. Rickets affects the cartilage of the epiphyseal growth plates in children, while osteomalacia affects the sites of bone turnover in children and adults. Although most cases of rickets and osteomalacia are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Rickets commonly presents with skeletal deformities and growth abnormalities, while osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Diagnosis is made based on a combination of clinical findings, laboratory tests and imaging. Treatment includes vitamin D, calcium, and phosphorus supplementation.

Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Molecular profiling of the cancer provides further distinction of the tumor's biological behavior, prognosis, and treatment options. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Regional and metastatic spread cause additional symptoms and complications depending on the location and organ(s) affected. Related paraneoplastic syndromes include hypercalcemia, hyponatremia, Lambert-Eaton syndrome, Cushing's syndrome, polydermatomyositis, and dermatomyositis. Definitive diagnosis and staging are made by biopsy, genetic mutation with biomarker testing, and imaging. Management is guided by the cancer stage and associated molecular profile. Lung cancer carries an overall poor prognosis.

Paget's disease of bone (PDB), also known historically as osteitis deformans, is a focal disorder of bone metabolism that affects about 2%–9% of people. Commonly affected areas include the skull, spine, pelvis, and long bones of the lower extremity. The 2 main clinical manifestations of Paget's disease are bone pain and the consequences of bone deformities, such as fractures, osteoarthritis, or nerve impingement. The management includes bisphosphonates, calcitonin, and surgery for the management of fractures, deformities, and complications. The prognosis for PDB is good, especially if treatment is started before major changes have occurred in the bones.

Pulmonary, or chest, imaging includes imaging of the lungs and surrounding structures in the thorax. Imaging of the chest represents a substantial portion of the imaging tests that are routinely performed. Common imaging methods include X-ray, CT, MRI, and ultrasonography (US). Each imaging method has advantages and disadvantages. Radiology exams, once completed, are read and interpreted by board-certified, fellowship-trained radiologists; however, most physicians should know the basics of how to interpret these images.

Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Patients can exhibit symptoms from neuromuscular irritability (tetany, Chvostek sign, Trousseau sign) to cardiovascular dysfunction (arrhythmia). Confirmation of hypocalcemia is required with correction of the value depending on albumin level or ionized calcium (the metabolically active form), followed by PTH level, and determination of the underlying cause. Correction of calcium is dictated by the degree of severity of hypocalcemia. In severe cases, IV calcium administration is required. Treatment of the underlying cause is recommended.