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In the animal kingdom there also exists a non-pathological form of osteosclerosis, resulting in unusually solid bone structure with little to no marrow. It is often seen in aquatic vertebrates, especially those living in shallow waters, providing ballast as an adaptation for an aquatic lifestyle. It makes bones heavier, but also more fragile. In those animal groups osteosclerosis often occurs together with bone thickening (pachyostosis). This joint occurrence is called pachyosteosclerosis.

Osteosclerosis is a disorder that is characterized by abnormal hardening of bone and an elevation in bone density. It may predominantly affect the medullary portion and/or cortex of bone. Plain radiographs are a valuable tool for detecting and classifying osteosclerotic disorders. It can manifest in localized or generalized osteosclerosis. Localized osteosclerosis can be caused by Legg–Calvé–Perthes disease, sickle-cell disease and osteoarthritis among others. Osteosclerosis can be classified in accordance with the causative factor into acquired and hereditary.

Approximately eight to 40 children are born in the United States each year with the malignant infantile type of osteopetrosis. One in every 100,000 to 500,000 individuals is born with this form of osteopetrosis. Higher rates have been found in Denmark and Costa Rica. Males and females are affected in equal numbers.

The adult type of osteopetrosis affects about 1,250 individuals in the United States. One in every 200,000 individuals is affected by the adult type of osteopetrosis. Higher rates have been found in Brazil. Males and females are affected in equal numbers.

The odds are greater in the Russian region of Mari El (1 of every 14,000 newborns) and much greater in Chuvashia (1 of every 3,500—4,000 newborns) due to genetic features of the Mari people and Chuvash people, respectively.

The only effective line of treatment for malignant infantile osteopetrosis is hematopoietic stem cell transplantation. It has been shown to provide long-term disease-free periods for a significant percentage of those treated; can impact both hematologic and skeletal abnormalities; and has been used successfully to reverse the associated skeletal abnormalities.

Radiographs of at least one case with malignant infantile osteopetrosis have demonstrated bone remodeling and recanalization of medullar canals following hematopoietic stem cell transplantation. This favorable radiographic response could be expected within one year following the procedure - nevertheless, primary graft failure can prove fatal.

Axial osteomalacia is a rare osteosclerotic disorder characterized by axial skeleton pain, coarsening of the trabecular bone pattern on radiographs of the axial but not appendicular skeleton.

Osteogenesis imperfecta is a rare condition in which bones break easily. There are multiple genetic mutations in different genes for collagen that may result in this condition. It can be treated with some drugs to promote bone growth, by surgically implanting metal rods in long bones to strengthen them, and through physical therapy and medical devices to improve mobility.

The disorder is progressive, with the ultimate severity of symptoms often depending on age of onset. In severe cases amputation has been performed when conservative measures such as physical therapy and regional anesthetics have been ineffective.

Melorheostosis is a medical developmental disorder and mesenchymal dysplasia in which the bony cortex widens and becomes hyperdense in a sclerotomal distribution. The condition begins in childhood and is characterized by thickening of the bones. Pain is a frequent symptom and the bone can have the appearance of dripping candle wax.

Osteochondrodysplasia or skeletal dysplasia is a general term for a disorder of the development (dysplasia) of bone ("osteo") and cartilage ("chondro").

Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia.

Pachyosteosclerosis is a combination of thickening (pachyostosis) and densification (osteosclerosis) of bones. It makes bones more heavy, but also more fragile. The condition often occurs in aquatic vertebrates, especially those living in shallow waters, creating ballast as an adaptation for maintaining neutral buoyancy and horizontal trim. It is in no way pathological. To resist roll, it frequently is found especially in ventral bones, whereas concentration near the lungs helps in maintaining trim.

Examples of animals showing pachyosteosclerosis are seacows (dugongs and manatees), the extinct Plesiosauria and Mesosauria and extinct aquatic sloths.

The differential diagnosis of malignant infantile osteopetrosis includes other genetic skeletal dysplasias that cause osteosclerosis. They are collectively known as osteosclerosing dysplasias. The differential diagnosis of genetic osteosclerosing dysplasias including infantile osteopetrosis has been tabulated and illustrated in literature citations.

- Neuropathic infantile osteopetrosis

- Infantile osteopetrosis with renal tubular acidosis

- Infantile osteopetrosis with immunodeficiency

- IO with leukocyte adhesion deficiency syndrome (LAD-III)

- Intermediate osteopetrosis

- Autosomal dominant osteopetrosis (Albers-Schonberg)

- Pyknodysostosis (osteopetrosis acro-osteolytica)

- Osteopoikilosis (Buschke–Ollendorff syndrome)

- Osteopathia striata with cranial sclerosis

- Mixed sclerosing bone dysplasia

- Progressive diaphyseal dysplasia (Camurati–Engelmann disease)

- SOST-related sclerosing bone dysplasias

Till date about 18 cases of Spondylocostal dysostosis have been reported in literature.

In 1968, Dr. David Rimoin and colleagues in Baltimore first distinguished between the two major presentations of Jarcho-Levin. Both conditions were characterized as failures of proper vertebral segmentation. However, the condition within the family described in their article appeared to be inherited in an autosomal dominant fashion and had a less severe course than that reported by other investigators. They specified their condition as spondylocostal dysplasia, which has since become known as spondylocostal dysostosis. The subtype of Jarcho-Levin with which they contrasted their reported cases to is now known as spondylothoracic dysplasia.

There is not a specific theory behind the etiology of the unicameral bone cyst, however, according to many researchers and doctors, there is a commonly known theory hypothesized by Jonathan Cohen in 1970. Cohen studied interstitial fluid in six children undergoing treatment for unicameral bone cysts. He believed that the chemical composition of the fluid found in the bone cyst was similar to the chemical make-up in serum. Cohen theorized that the unicameral bone cyst occurs when interstitial fluids in cancellous bones quickly accumulate in one region from blockage.

One of the other theories is that the cysts result from a disorder of the growth plate. Another is that the cysts result from problems with circulation that are caused by a developmental anomaly in the veins of the affected bone. The role trauma plays in the development of these cysts is unknown. Some speculate that repeated trauma puts the bone at risk for developing a bone cyst. This, however, has not been proven.

Most cases of SPB progress to multiple myeloma within 2–4 years of diagnosis, but the overall median survival for SPB is 7–12 years. 30–50% of extramedullary plasmacytoma cases progress to multiple myeloma with a median time of 1.5–2.5 years. 15–45% of SPB and 50–65% of extramedullary plasmacytoma are disease free after 10 years.

Plasmacytomas are a rare form of cancer. SPB is the most common form of the disease and accounts for 3-5% of all plasma cell malignancies. The median age at diagnosis for all plasmacytomas is 55. Both SPB and extramedullary plasmacytoma are more prevalent in males; with a 2:1 male to female ratio for SPB and a 3:1 ratio for extramedullary plasmacytoma.

Most unicameral bone cysts do not cause any symptoms and are discovered as accidental findings on radiographs or CT scans made for other reasons. Large lesions can cause nearby areas of bone to thin, which may result in a fracture and cause pain.

Bone mineral density decreases with increasing age. Osteoporotic bone loss can be prevented through an adequate intake of vitamin C and vitamin D, coupled with exercise and by being a non-smoker. A study by Cheng et al. in 1997, showed that greater bone density indicated less risk for fractures in the calcaneus.

Idiopathic osteosclerosis is a condition which may be found around the roots of a tooth. It is usually painless and found during routine radiographs. It appears as a radiopaque (light area) around a tooth, usually a premolar or molar. There is no sign of inflammation of the tooth.

Condensing osteitis, sclerosing osteomyelitis, cementoblastoma, hypercementosis, Exostoses (tori).

Condensing osteitis may resemble idiopathic osteosclerosis, however, associated teeth are always nonvital in condensing osteitis.

In 1991, Kathol conducted a study which showed a correlation between calcaneal insufficiency avulsion fractures (a fracture in which the Achilles tendon removes a portion of the bone as it rescinds) and diabetes mellitus. The diabetic population is more susceptible to the risks of fracture and potential healing complications and infection that may lead to limb amputation. Diabetes can be regulated and prevented through diet and exercise.

Jefferson fracture is often caused by an impact or load on the back of the head, and are frequently associated with diving into shallow water, impact against the roof of a vehicle and falls, and in children may occur due to falls from playground equipment. Less frequently, strong rotation of the head may also result in Jefferson fractures.

Jefferson fractures are extremely rare in children, but recovery is usually complete without surgery.

The etiology of the Galeazzi fracture is thought to be a fall that causes an axial load to be placed on a hyperpronated forearm. However, researchers have been unable to reproduce the mechanism of injury in a laboratory setting.

After the injury, the fracture is subject to deforming forces including those of the brachioradialis, pronator quadratus, and thumb extensors, as well as the weight of the hand. The deforming muscular and soft-tissue injuries that are associated with this fracture cannot be controlled with plaster immobilization.

Axial spondyloarthritis (also often referred to as axSpA) is a chronic, autoinflammatory disease predominantly affecting the axial skeleton (sacroiliac joints and spine). The most known member of the axial spondyloarthritis disease family is ankylosing spondylitis. Axial spondyloarthritis is an umbrella term that has been introduced in the year 2009 to characterize a diverse disease family that share clinical and genetic features, such as the involvement of the axial skeleton. The expression was introduced in order to unify (1) less severe forms of spondylitis, (2) the early phase of ankylosing spondylitis as well as (3) ankylosing spondylitis itself into one term.