The cause of spondylolysis remains unknown, however many factors are thought to contribute to its development. The condition is present in up to 6% of the population, majority of which usually present asymptomatically. Research supports that there are hereditary and acquired risk factors that can make one more susceptible to the defect. The disorder is generally more prevalent in males compared to females, and tends to occur earlier in males due to their involvement in more strenuous activities at a younger age. In a young athlete, the spine is still growing which means there are many ossification centers, leaving points of weakness in the spine. This leaves young athletes at increased risk, particularly when involved in repetitive hyperextension and rotation across the lumbar spine. Spondylolysis is a common cause of low back pain in preadolescents and adolescent athletes, as it accounts for about 50% of all low back pain. It is believed that both repetitive trauma and an inherent genetic weakness can make an individual more susceptible to spondylolysis.

Sports involving repetitive or forceful hyperextension of the spine, especially when combined with rotation are the main mechanism of injury for spondylolysis. The stress fracture of the pars interarticularis occurs on the side opposite to activity. For instance, for a right-handed player, the fracture occurs on the left side of the vertebrae.

Spondylolysis has a higher occurrence in the following activities:

- Baseball

- Tennis

- Diving

- Cheerleading

- Gymnastics

- Football

- Soccer

- Wrestling

- Weightlifting

- Roller Derby

- Cricket

- Pole Vault

- Rugby

- Volleyball

- Gym

- Ultimate Frisbee (especially during impact from laying out)

Although this condition can be caused by repetitive trauma to the lumbar spine in strenuous sports, other risk factors can also predispose individuals to spondylolsis. Males are more commonly affected by spondylolysis than females. In one study looking at youth athletes, it was found that the mean age of individuals with spondylolisthesis was 20 years of age. Spondylolysis also runs in families suggesting a hereditary component such as a predisposition to weaker vertebrae.

Degenerative disc disease (DDD) describes the natural breakdown of an intervertebral disc of the spine. Despite its name, DDD is not considered a disease, nor is it progressively degenerative. On the contrary, disc degeneration is often the effect of natural daily stresses and minor injuries that cause spinal discs to gradually lose water as the anulus fibrosus, or the rigid outer shell of a disc, weakens. As discs weaken and lose water, they begin to collapse. This can result in pressure being put on the nerves in the spinal column, causing pain and weakness.

While not always symptomatic, DDD can cause acute or chronic low back or neck pain as well as nerve pain depending on the location of the affected disc and the amount of pressure it places on the surrounding nerve roots.

The typical radiographic findings in DDD are black discs, disc space narrowing, vacuum disc, end plate sclerosis, and osteophyte formation.

DDD can greatly affect quality of life. Disc degeneration is a disease of micro/macro trauma and of aging, and though for most people is not a problem, in certain individuals a degenerated disc can cause severe chronic pain if left untreated.

The term, degenerative disc disease is a slight misnomer because it is not technically a disease, nor is it strictly degenerative. It is not considered a disease because degenerative changes in the spine are natural and common in the general population.

There is a disc between each of the vertebrae in the spine. A healthy, well-hydrated disc will contain a great deal of water in its center, known as the nucleus pulposus, which provides cushioning and flexibility for the spine. Much of the mechanical stress that is caused by everyday movements is transferred to the discs within the spine and the water content within them allows them to effectively absorb the shock. At birth, a typical human nucleus pulposus will contain about 80% water. However natural daily stresses and minor injuries can cause these discs to gradually lose water as the anulus fibrosus, or the rigid outer shell of a disc, weakens.

This water loss makes the discs less flexible and results in the gradual collapse and narrowing of the gap in the spinal column. As the space between vertebrae gets smaller, extra pressure can be placed on the discs causing tiny cracks or tears to appear in the anulus. If enough pressure is exerted, it's possible for the nucleus pulposus material to seep out through the tears in the anulus and can cause what is known as a herniated disc.

As the two vertebrae above and below the affected disc begin to collapse upon each other, the facet joints at the back of the spine are forced to shift which can affect their function.

Additionally, the body can react to the closing gap between vertebrae by creating bone spurs around the disc space in an attempt to stop excess motion. This can cause issues if the bone spurs start to grow into the spinal canal and put pressure on the spinal cord and surrounding nerve roots as it can cause pain and affect nerve function. This condition is called spinal stenosis.

For women, there is good evidence that menopause and related estrogen-loss are associated with lumbar disc degeneration, usually occurring during the first 15 years of the climacteric. The potential role of sex hormones in the etiology of degenerative skeletal disorders is being discussed for both genders.

Degenerative disc disease can also occur in other mammals besides humans; it is a common problem in several dog variants and attempts to remove this disease from dog populations have lead to several crosses, such as the Chiweenie.