The major symptoms of OFC are bone pain or tenderness, bone fractures, and skeletal deformities such as bowing of the bones. The underlying hyperparathyroidism may cause kidney stones, nausea, constipation, fatigue and weakness. X-rays may indicate thin bones, fractures, bowing, and cysts. Fractures are most commonly localized in the arms, legs, or spine.

The addition of weight loss, appetite loss, vomiting, polyuria, and polydipsia to the aforementioned symptoms may indicate that OFC is the result of parathyroid carcinoma. Parathyroid carcinoma, an uncommon cancer of the parathyroid glands, is generally indicated by serum calcium levels higher than usual, even in comparison to the high serum calcium levels that OFC generally presents with. Symptoms are also often more severe. Generally, the presence of a palpable neck mass is also indicative of the cancer, occurring in approximately 50% of sufferers, but virtually nonexistent in individuals with OFC with a different origin.

Renal osteodystrophy may exhibit no symptoms; if it does show symptoms, they include:

- Bone pain

- Joint pain

- Bone deformation

- Bone fracture

- The broader concept of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not only associated with fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients (the so-called bone-vascular axis). These clinical consequences are acquiring such an importance that scientific working groups (such as the ERA-EDTA CKD-MBD Working Group) or international initiatives are trying to promote research in the field including basic, translational and clinical research.

Osteitis fibrosa cystica is defined as the classic skeletal manifestation of advanced hyperparathyroidism. Under the ICD-10 classification system, established by the World Health Organization, OFC is listed under category E21.0, primary hyperparathyroidism.

To confirm the diagnosis, renal osteodystrophy must be characterized by determining bone turnover, mineralization, and volume (TMV system) (bone biopsy). All forms of renal osteodystrophy should also be distinguished from other bone diseases which may equally result in decreased bone density (related or unrelated to CKD):

- osteoporosis

- osteopenia

- osteomalacia

- brown tumor should be considered as the top-line diagnosis if a mass-forming lesion is present.

Osteodystrophy is any dystrophic growth of the bone. It is defective bone development that is usually attributable to renal disease or to disturbances in calcium and phosphorus metabolism.

One form is renal osteodystrophy.

Pseudopseudohypoparathyroidism can be best understood by comparing it to other conditions:

Hormone resistance is not present in pseudopseudohypoparathyroidism. Short stature may be present. Obesity is less common in pseudopseudohypoparathyroidism than in pseudohypoparathyroidism. Osteoma cutis may be present.

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is one of the many complications associated with chronic kidney disease. It represents a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:

- Abnormalities of calcium, phosphorus (phosphate), parathyroid hormone, or vitamin D metabolism

- Abnormalities in bone turnover, mineralization, volume, linear growth, or strength

- Vascular or other soft-tissue calcification

CKD-MBD explains, at least in part, the high morbidity and mortality of CKD patients, linking kidney and bone disease with cardiovascular complications. It is a matter of discussion whether CKD-MBD may be considered a real syndrome or not.

CKD-MBD broadens the "old" concept of "renal osteodystrophy", which now should be restricted to describing the "bone pathology" associated with CKD. Thus, renal osteodystrophy is currently considered "one" measure of the skeletal component of the systemic disorder of CKD–MBD that is quantifiable by histomorphometry of bone biopsy.

The disorder is characterized by the following:

Individuals with Albright hereditary osteodystrophy exhibit short stature, characteristically shortened fourth and fifth metacarpals, rounded facies, and often mild intellectual deficiency. Albright hereditary osteodystrophy is commonly known as pseudohypoparathyroidism because the kidney responds as if parathyroid hormone were absent. Blood levels of parathyroid hormone are elevated in pseudohypoparathyroidism due to the hypocalcemia

Symptoms depend on whether the hyperparathyroidism is the result of parathyroid overactivity or secondary.

In primary hyperparathyroidism about 75% of people have no symptoms. The problem is often picked up during blood work for other reasons via a raised calcium. Many other people only have non-specific symptoms. Symptoms directly due to hypercalcemia are relatively rare, being more common in patients with malignant hypercalcemia. If present, common manifestations of hypercalcemia include weakness and fatigue, depression, bone pain, muscle soreness (myalgias), decreased appetite, feelings of nausea and vomiting, constipation, polyuria, polydipsia, cognitive impairment, kidney stones (See Foot Note) and osteoporosis. A history of acquired racquet nails (brachyonychia) may be indicative of bone resorption. Parathyroid adenomas are very rarely detectable on clinical examination. Surgical removal of a parathyroid tumor eliminates the symptoms in most patients.

In secondary hyperparathyroidism the parathyroid gland is behaving normally; clinical problems are due to bone resorption and manifest as bone syndromes such as rickets, osteomalacia and renal osteodystrophy.

The causes of adult osteomalacia are varied, but ultimately result in a vitamin D deficiency:

Osteomalacia is a generalized bone condition in which there is inadequate mineralization of the bone. Many of the effects of the disease overlap with the more common osteoporosis, but the two diseases are significantly different. There are two main causes of osteomalacia:

1. insufficient calcium absorption from the intestine because of lack of dietary calcium or a deficiency of, or resistance to, the action of vitamin D

2. phosphate deficiency caused by increased renal losses.

Symptoms:

Osteomalacia in adults starts insidiously as aches and pains in the lumbar (lower back) region and thighs before spreading to the arms and ribs. The pain is symmetrical, non-radiating and accompanied by sensitivity in the involved bones. Proximal muscles are weak, and there is difficulty in climbing up stairs and getting up from a squatting position.

As a result of demineralization, the bones become less rigid. Physical signs include deformities like triradiate pelvis and lordosis. The patient has a typical "waddling" gait. However, these physical signs may derive from a previous osteomalacial state, since bones do not regain their original shape after they become deformed.

Pathologic fractures due to weight bearing may develop. Most of the time, the only alleged symptom is chronic fatigue, while bone aches are not spontaneous but only revealed by pressure or shocks.It differs from renal osteodystrophy, where the latter shows hyperphosphatemia.

Secondary hyperparathyroidism is due to physiological (i.e. appropriate) secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels). The most common causes are vitamin D deficiency (caused by lack of sunlight, diet or malabsorption) and chronic kidney failure.

Lack of vitamin D leads to reduced calcium absorption by the intestine leading to hypocalcemia and increased parathyroid hormone secretion. This increases bone resorption.

In chronic kidney failure the problem is more specifically failure to convert vitamin D to its active form in the kidney. The bone disease in secondary hyperparathyroidism caused by renal failure is termed renal osteodystrophy.

Pseudopseudohypoparathyroidism (PPHP) is an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation. It is more properly Albright hereditary osteodystrophy although without resistance of parathyroid hormone frequently seen in that affliction. The term pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism type 1a, but has (unexpected for the phenotype) normal labs including Calcium and PTH.

It can be considered a variant of Albright hereditary osteodystrophy, or pseudohypoparathyroidism type 1A, as they present with the same constellation of signs and symptoms, including short stature, brachydactyly, subcutaneous calcification, and obesity.

The diagnosis of Albright's hereditary osteodystrophy is based on the following exams below:

- CBC

- Urine test

- MRI

Signs and symptoms include ectopic calcification, secondary hyperparathyroidism, and renal osteodystrophy. Abnormalities in phosphate metabolism such as hyperphosphatemia are included in the definition of the new chronic kidney disease-mineral and bone disorder (CKD-MBD).

Hyperphosphatemia is an electrolyte disturbance in which there is an abnormally elevated level of phosphate in the blood. Often, calcium levels are lowered (hypocalcemia) due to precipitation of phosphate with the calcium in tissues. Average phosphorus levels should be between 0.81 mmol/litre and 1.45 mmol/litre.

Fractures are the most dangerous aspect of osteoporosis. Debilitating acute and chronic pain in the elderly is often attributed to fractures from osteoporosis and can lead to further disability and early mortality. These fractures may also be asymptomatic. The most common osteoporotic fractures are of the wrist, spine, shoulder and hip. The symptoms of a vertebral collapse ("compression fracture") are sudden back pain, often with radicular pain (shooting pain due to nerve root compression) and rarely with spinal cord compression or cauda equina syndrome. Multiple vertebral fractures lead to a stooped posture, loss of height, and chronic pain with resultant reduction in mobility.

Fractures of the long bones acutely impair mobility and may require surgery. Hip fracture, in particular, usually requires prompt surgery, as serious risks are associated with it, such as deep vein thrombosis and pulmonary embolism, and increased mortality.

Fracture risk calculators assess the risk of fracture based upon several criteria, including BMD, age, smoking, alcohol usage, weight, and gender. Recognized calculators include FRAX and Dubbo.

The term "established osteoporosis" is used when a broken bone due to osteoporosis has occurred. Osteoporosis is a part of frailty syndrome.

Osteoporosis itself has no symptoms; its main consequence is the increased risk of bone fractures. Osteoporotic fractures occur in situations where healthy people would not normally break a bone; they are therefore regarded as fragility fractures. Typical fragility fractures occur in the vertebral column, rib, hip and wrist.

Brown tumours consist of fibrous tissue, woven bone and supporting vasculature, but no matrix. The osteoclasts consume the trabecular bone that osteoblasts lay down and this front of reparative bone deposition followed by additional resorption can expand beyond the usual shape of the bone, involving the periosteum thus causing bone pain. The characteristic brown coloration results from hemosiderin deposition into the osteolytic cysts. Hemosiderin deposition is not a distinctive feature of brown tumors; it may also be seen in giant cell tumors of the bone.

Brown tumors may be rarely associated with ectopic parathyroid adenomas or end stage renal osteodystrophy.

It is well-known that as kidney function declines, there is a progressive deterioration in mineral homeostasis, with a disruption of normal serum and tissue concentrations of phosphorus and calcium, and changes in circulating levels of hormones. These include parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH) vitamin D; calcidiol), 1,25-dihydroxyvitamin D (1,25(OH)2 vitamin D; calcitriol), and other vitamin D metabolites, fibroblast growth factor 23 (FGF-23), and growth hormone. Beginning in CKD stage 3, the ability of the kidneys to appropriately excrete a phosphate load is diminished, leading to hyperphosphatemia, elevated PTH (secondary hyperparathyroidism), and decreased 1,25(OH)2 vitamin D with associated elevations in the levels of FGF-23. The conversion of 25(OH) vitamin D to 1,25(OH)2 vitamin D is impaired, reducing intestinal calcium absorption and increasing PTH. The kidney fails to respond adequately to PTH, which normally promotes phosphaturia and calcium reabsorption, or to FGF-23, which also enhances phosphate excretion. In addition, there is evidence at the tissue level of a downregulation of vitamin D receptor and of resistance to the actions of PTH. Therapy is generally focused on correcting biochemical and hormonal abnormalities in an effort to limit their consequences.

The mineral and endocrine functions disrupted in CKD are critically important in the regulation of both initial bone formation during growth (bone modeling) and bone structure and function during adulthood (bone remodeling). As a result, bone abnormalities are found almost universally in patients with CKD requiring dialysis (stage 5D), and in the majority of patients with CKD stages 3–5. More recently, there has been an increasing concern of extraskeletal calcification that may result from the deranged mineral and bone metabolism of CKD and from the therapies used to correct these abnormalities.

Numerous cohort studies have shown associations between disorders of mineral metabolism and fractures, cardiovascular disease, and mortality. These observational studies have broadened the focus of CKD-related mineral and bone disorders (MBDs) to include cardiovascular disease (which is the leading cause of death in patients at all stages of CKD). All three of these processes (abnormal mineral metabolism, abnormal bone, and extraskeletal calcification) are closely interrelated and together make a major contribution to the morbidity and mortality of patients with CKD. The traditional definition of renal osteodystrophy did not accurately encompass this more diverse clinical spectrum, based on serum biomarkers, noninvasive imaging, and bone abnormalities. The absence of a generally accepted definition and diagnosis of renal osteodystrophy prompted Kidney Disease: Improving Global Outcomes (KDIGO)] to sponsor a controversies conference, entitled "Definition, Evaluation, and Classification of Renal Osteodystrophy", in 2005. The principal conclusion was that the term "CKD–Mineral and Bone Disorder (CKD–MBD)" should now be used to describe the "broader clinical syndrome encompassing mineral, bone, and calcific cardiovascular abnormalities that develop as a complication of CKD".

Pathologic fractures in children and adolescents can result from a diverse array of disorders namely; metabolic, endocrine, neoplastic, infectious, immunologic, and genetic skeletal dysplasias.

- Osteogenesis imperfecta

- Primary hyperparathyroidism

- Simple bone cyst

- Aneurismal bone cyst

- Disuse osteoporosis

- Chronic osteomyelitis

- Osteogenesis imperfecta

- Rickets

- Renal osteodystrophy

- Malignant infantile osteopetrosis

- juvenile osteoporosis

- juvenile rheumatoid arthritis

In circumstances where other pathologies are excluded (for example, cancer), a pathologic fracture is diagnostic of osteoporosis irrespective of bone mineral density.

The brown tumor is a bone lesion that arises in settings of excess osteoclast activity, such as hyperparathyroidism. It is not a true neoplasm, as the term "tumor" suggests; however, it may mimic a true neoplasm. It most commonly affects the maxilla and mandible, though any bone may be affected. Brown tumours are radiolucent on x-ray.

Usually, a SCFE causes groin pain, but it may cause pain in only the thigh or knee, because the pain may be referred along the distribution of the obturator nerve. The pain may occur on both sides of the body (bilaterally), as up to 40 percent of cases involve slippage on both sides. After a first SCFE, when a second SCFE occurs on the other side, it typically happens within one year after the first SCFE. About 20 percent of all cases include a SCFE on both sides at the time of presentation.

Signs of a SCFE include a waddling gait, decreased range of motion. Often the range of motion in the hip is restricted in internal rotation, abduction, and flexion. A person with a SCFE may prefer to hold their hip in flexion and external rotation.

CKD is initially without specific symptoms and is generally only detected as an increase in serum creatinine or protein in the urine. As the kidney function decreases:

- Blood pressure is increased due to fluid overload and production of vasoactive hormones created by the kidney via the renin-angiotensin system, increasing one's risk of developing hypertension and/or suffering from congestive heart failure.

- Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). Due to its high systemic circulation, urea is excreted in eccrine sweat at high concentrations and crystallizes on skin as the sweat evaporates ("uremic frost").

- Potassium accumulates in the blood (hyperkalemia with a range of symptoms including malaise and potentially fatal cardiac arrhythmias). Hyperkalemia usually does not develop until the glomerular filtration rate falls to less than 20–25 ml/min/1.73 m, at which point the kidneys have decreased ability to excrete potassium. Hyperkalemia in CKD can be exacerbated by acidemia (which leads to extracellular shift of potassium) and from lack of insulin.

- Erythropoietin synthesis is decreased causing anemia.

- Fluid volume overload symptoms may range from mild edema to life-threatening pulmonary edema.

- Hyperphosphatemia, due to reduced phosphate excretion, follows the decrease in glomerular filtration. Hyperphosphatemia is associated with increased cardiovascular risk, being a direct stimulus to vascular calcification. Moreover, circulating concentrations of fibroblast growth factor-23 (FGF-23) increase progressively as the renal capacity for phosphate excretion declines, but this adaptative response may also contribute to left ventricular hypertrophy and increased mortality in CKD patients.

- Hypocalcemia, due to 1,25 dihydroxyvitamin D deficiency (caused by stimulation of FGF-23 and reduction of renal mass), and resistance to the calcemic action of parathyroid hormone. Osteocytes are responsible for the increased production of FGF-23, which is a potent inhibitor of the enzyme 1-alpha-hydroxylase (responsible for the conversion of 25-hydroxycholecalciferol into 1,25 dihydroxyvitamin D). Later, this progresses to secondary hyperparathyroidism, renal osteodystrophy, and vascular calcification that further impairs cardiac function. An extreme consequence is the occurrence of the rare condition named calciphylaxis.

- The concept of chronic kidney disease-mineral bone disorder (CKD-MBD) currently describes a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD manifested by either "one or a combination" of: 1) abnormalities of calcium, phosphorus (phosphate), parathyroid hormone, or vitamin D metabolism; 2) abnormalities in bone turnover, mineralization, volume, linear growth, or strength (renal osteodystrophy); and 3) vascular or other soft-tissue calcification. CKD-MBD has been associated to poor hard outcomes.

- Metabolic acidosis (due to accumulation of sulfates, phosphates, uric acid etc.) may cause altered enzyme activity by excess acid acting on enzymes; and also increased excitability of cardiac and neuronal membranes by the promotion of hyperkalemia due to excess acid (acidemia). Acidosis is also due to decreased capacity to generate enough ammonia from the cells of the proximal tubule.

- Iron deficiency anemia, which increases in prevalence as kidney function decreases, is especially prevalent in those requiring haemodialysis. It is multifactoral in cause, but includes increased inflammation, reduction in erythropoietin, and hyperuricemia leading to bone marrow suppression.

People with CKD suffer from accelerated atherosclerosis and are more likely to develop cardiovascular disease than the general population. Patients afflicted with CKD and cardiovascular disease tend to have significantly worse prognoses than those suffering only from the latter.

Sexual dysfunction is very common in both men and women with CKD. A majority of men have a reduced sex drive, difficulty obtaining an erection, and reaching orgasm, and the problems get worse with age. A majority of women have trouble with sexual arousal, and painful menstruation and problems with performing and enjoying sex are common.