Replacements of glycine with serine or cysteine are seen less often in fatal type II OI, while replacements with valine, aspartic acid, glutamic acid, or arginine are seen more often.At a larger scale, the relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness. Bone fractures occur because the stress state within collagen fibrils is altered at the locations of mutations, where locally larger shear forces lead to rapid failure of fibrils even at moderate loads because the homogeneous stress state normally found in healthy collagen fibrils is lost. OI is therefore a multi-scale phenomenon, where defects at the smallest levels of tissues (genetic, nano, micro) domino to affect the macro level of tissues. Diagnosis
Diagnosis is typically based on medical imaging, including plain X-rays, and symptoms. In severe OI, signs on medical imaging include abnormalities in all extremities and in the spine. As X-rays are often insensitive to the comparatively smaller bone density loss associated with type I OI, DEXA scans may be needed. : 1514 An OI diagnosis can be confirmed through DNA or collagen protein analysis, but in many cases, the occurrence of bone fractures with little trauma and the presence of other clinical features such as blue sclerae are sufficient for a diagnosis. A skin biopsy can be performed to determine the structure and quantity of type I collagen. While DNA testing can confirm the diagnosis, it cannot absolutely exclude it because not all mutations causing OI are yet known and/or tested for.
Chronic constipation is especially common,: 377  and is thought to be aggravated by an asymmetric pelvis (acetabular protrusion). : 377  Especially in childhood, OI-associated constipation may cause a feeling of fullness and associated food refusal, leading to malnutrition. : 377

Classification
There are two typing systems for OI in modern use. The first, created by David Sillence in 1979, classifies patients into four types, or syndromes, according to their clinical presentation, without taking into account the genetic cause of their disease. : 114–115  The second system expands on the Sillence model, but assigns new numbered types genetically as they are found. Therefore, people with OI can be described as having both a clinical type and a genetic type, which may or may not be equivalent.Type I is the most common, and 90% of cases result from mutations to either COL1A1 or COL1A2. Symptoms vary a lot between types, as well as vary from person to person, even in the same family.As of 2021, 21 types of OI have been defined:

Sillence types
Sillences four types have both a clinical and a genetic meaning; the descriptions below are clinical and can be applied to several genetic types of OI. When used to refer to a genetic as well as a clinical type, it indicates that the clinical symptoms are indeed caused by mutations in the COL1A1 or COL1A2 genes which are inherited in an autosomal dominant fashion. Type I
Collagen is of normal quality but is produced in insufficient quantities.