Osteogenesis Imperfecta

Osteogenesis imperfecta is an inherited disorder of connective tissue, in most cases caused by a fault in one of the two genes that direct the manufacture of type I collagen, the protein that forms the flexible framework on which bone mineral is laid down. When this collagen is abnormal in quality or reduced in quantity, the bone that forms around it is weak, thin and brittle. The result is a tendency to fracture with little or no force, together with features such as a bluish tint to the whites of the eyes, fragile teeth, loose joints, hearing loss in adult life, and short stature in the more severe forms.

The condition varies enormously in severity. A widely used framework, originally described by Sillence, divides it into several types, from a mild form compatible with a near-normal life to forms severe or lethal around the time of birth. This range matters for the spine, because the more severe the underlying bone fragility, the more pronounced and the earlier the spinal problems tend to be.

The vertebral bodies are built largely of the spongy, trabecular bone that osteogenesis imperfecta weakens most. Soft vertebrae compress and deform under the ordinary loads of standing and sitting; weak bone at the growth plates allows curves to develop and progress; and the bone of the skull base, itself softened, can gradually settle around the top of the spine. The spinal features of osteogenesis imperfecta are local expressions of the same underlying fragility.

One of the most characteristic spinal findings is the deformation of the vertebral bodies themselves. Because the bone is soft, the vertebrae do not always fracture in the sudden, dramatic way a long bone does. Instead they tend to yield gradually under load, so that the vertebral body loses height and changes shape.

The classic appearance is the biconcave vertebra, in which the upper and lower surfaces of the vertebral body are pressed inwards by the cushioning discs above and below, hollowing out the bone into a shape that has long been likened to the body of a codfish. This 'codfish' or 'fish vertebra' pattern is so typical that it is regarded as a hallmark of the condition on a side-on X-ray. The number of deformed, biconcave vertebrae has been used as an indicator of how severely the spine is affected. These vertebral changes are, in effect, compression fractures of soft bone, accumulating over years rather than occurring in a single moment, and they contribute to loss of height, stooped posture and the development of spinal curves.

Curvature of the spine is among the most frequent and troublesome spinal features. Scoliosis is reported across a wide range of frequencies, in some cohorts affecting the majority of patients, and it becomes both more common and more severe with the more severe forms of the condition. Excessive kyphosis frequently accompanies it, producing a combined kyphoscoliosis.

The mechanism is twofold. First, the accumulation of vertebral compression fractures and the wedging and biconcave deformation of the vertebral bodies physically distort the column, so that the curve grows out of the deformed building blocks themselves. Second, the underlying weakness of the bone and the abnormal growth at the vertebral growth plates allow curves to develop and progress. There is also growing interest in the role of disordered signalling pathways within bone. Crucially these curves tend to progress, and to continue progressing into and through adult life, more relentlessly than typical adolescent curves, driven by ongoing softening and fracture rather than by growth alone.

In ordinary adolescent scoliosis, a brace is a mainstay of non-operative management. In osteogenesis imperfecta the situation is different. The very fragility that defines the condition is the reason. A brace works by applying corrective pressure to the trunk and the rib cage. In osteogenesis imperfecta the ribs and the underlying bone are themselves soft and prone to fracture and deformation, so the pressure a brace exerts is poorly tolerated and can deform the chest wall rather than correct the spine. For this reason bracing is generally regarded in the published literature as ineffective at controlling curve progression in osteogenesis imperfecta, and as carrying its own risks to the fragile thorax.

At the very top of the spine, where the skull meets the neck, osteogenesis imperfecta produces one of its most serious and characteristic problems. The bone of the skull base is, like the rest of the skeleton, softened. Under the steady downward load of the head over many years, the soft skull base can gradually settle and the upper cervical spine, in particular the peg-like odontoid process of the second vertebra, can migrate upwards into the opening at the base of the skull. This upward settling is known as basilar invagination, or basilar impression, and a related flattening of the skull base is called platybasia.

This matters because the opening at the base of the skull is where the brainstem and the upper spinal cord pass. As the bone settles inward and upward, it can begin to crowd these vital structures and to obstruct the normal flow of cerebrospinal fluid. Basilar invagination is reported in a substantial minority of people with osteogenesis imperfecta, more so in the severe forms. Although many remain without symptoms for a long time, it can in some cases give rise to headache, neck pain, difficulty with balance and swallowing, weakness, and other signs of pressure on the brainstem and cord. The craniocervical junction is regarded as a region deserving particular attention in osteogenesis imperfecta.

At the lower end of the spine, osteogenesis imperfecta is associated with a higher than usual tendency to spondylolisthesis, the forward slippage of one vertebra upon the one below, most often at the junction between the lowest lumbar vertebra and the sacrum. Studies of children and young people with the condition have reported rates of spondylolysis and of spondylolisthesis that exceed those seen in the general population.

The bony bridges and pedicles that normally lock a vertebra in position can fracture, elongate or give way under load, allowing slippage to occur. There is a recognised association between slippage at the lumbosacral junction and fracture of the fifth lumbar vertebra, with one analysis reporting that the great majority of those with spondylolisthesis had sustained such a fracture and that the presence of slippage roughly doubled the likelihood of it. Unusual patterns are also described, including extreme elongation of the pedicles that allows a vertebra to slip forward while the back of the spine is left behind.

When spinal surgery becomes necessary, it presents distinctive difficulties. The central problem is mechanical: the instruments used to correct and hold the spine, principally screws placed into the pedicles, must grip bone that is soft and offers little purchase. As a result, screws may pull out of the bone, the bone around them may crumble, the metalwork may cut through or dislodge, and the correction achieved at operation may be lost over the months and years that follow. The bone may even fracture during the manoeuvres of surgery itself.

Surgeons describe a range of strategies adapted to fragile bone: spreading the load across many anchor points rather than a few, using image guidance to place screws as accurately as possible in distorted anatomy, and augmenting the grip of screws with bone cement, which is injected to fill and reinforce the soft bone around the implant. Even so, the published surgical series report higher rates of implant-related complications and of loss of correction than would be expected in ordinary spinal deformity surgery.

A major development has been the use of bisphosphonates, a family of drugs that act on bone by slowing the cells that break it down, thereby allowing bone mass to build up. Used widely in children with the condition, often given by infusion, they have been shown to increase bone density, to reduce the rate of fractures, and to reshape and partially restore the height of collapsed vertebral bodies.

The evidence regarding the effect of bisphosphonates specifically on spinal curvature is more nuanced. Some studies have reported that treatment, particularly when started early and in certain types of the condition, is associated with a slower rate of scoliosis progression, while others have found no clear effect on whether a curve ultimately progresses to the point of needing surgery. Because bisphosphonates act by suppressing the natural turnover of bone, they can, in theory, slow the healing of fractures and of the cuts made in bone during an operation, and the literature accordingly discusses the timing of treatment around surgery, sometimes describing a planned pause.

Plain X-rays of the whole spine, taken standing where possible, are the foundation, used to measure the angle of any curve, to document the height and shape of the vertebral bodies, and to look for slippage at the lower spine. CT gives a precise account of the bony anatomy and is important for understanding distorted vertebrae and for examining the craniocervical junction. MRI shows the brainstem, the spinal cord and the cerebrospinal fluid spaces, and is the means by which any compression of these structures is assessed. Bone density measurement, typically by a DEXA scan, gauges the underlying fragility, though in children the result has to be interpreted with care using age- and size-adjusted scores.

The evidence base is built largely on observational studies, surgical case series, expert reviews and consensus, rather than on large randomised trials. Medical care of the bone is described as the foundation. Bisphosphonate treatment, alongside attention to general bone health, nutrition and physical activity, is reported to strengthen the vertebrae, reduce fracture and partially restore vertebral height. For curvature, the literature consistently notes that bracing is of limited value because the fragile thorax tolerates it poorly, and that monitoring of curve progression is central. Surgery for scoliosis or kyphosis is generally considered for severe and progressive curves, balanced against the fragility of the bone and the difficulty of fixation. For the craniocervical junction, the literature describes careful surveillance of basilar invagination, with intervention reserved for cases where there is progression or signs of pressure on the brainstem and spinal cord.

The outlook for the spine in osteogenesis imperfecta varies as widely as the condition itself, tracking closely with its severity. In milder forms, spinal involvement may be limited and slowly progressive. In more severe forms, curvature and vertebral deformity tend to appear earlier, to be more pronounced, and to progress more relentlessly, and the craniocervical junction warrants particular vigilance. Medical treatment of the bone, and bisphosphonates in particular, has improved the strength of the vertebrae and reduced fracture, changing the natural history for the better. Any individual outlook is a matter for assessment by the treating team.

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This information is for general patient education and is not a substitute for an individual consultation. Always seek personalised advice from a qualified spinal specialist.