Radiological, biochemical and hereditary evidence of two types of autosomal dominant osteopetrosis

Bollerslev, Jens; Andersen, Poul Erik

doi:10.1016/8756-3282(88)90021-x

Cited by 171 publications

(115 citation statements)

References 13 publications

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“…The condition is generally asymptomatic or presents with mild symptoms and with no increase in fracture risk. (11) Only a few studies have been published on bone structure in Lrp5-HBM that show increased cortical and trabecular thickness. (7,(12)(13)(14)(15)(16) The aims of the present study were to evaluate bone mass, geometry, structure, and markers of bone turnover in a large cohort of patients with HBM phenotype due to gain-of-function mutations in Lrp5 by HR-pQCT and to assess whether these changes correlate to serum serotonin and age.…”

Section: J Jbmrmentioning

confidence: 99%

Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high-bone-mass phenotype due to a mutation in Lrp5

Frost

Andersen

Gossiel

et al. 2011

Journal of Bone and Mineral Research

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Patients with an activation mutation of the Lrp5 gene exhibit high bone mass (HBM). Limited information is available regarding compartment-specific changes in bone. The relationship between the phenotype and serum serotonin is not well documented. To evaluate bone, serotonin, and bone turnover markers (BTM) in Lrp5-HBM patients, we studied 19 Lrp5-HBM patients (T253I) and 19 ageand sex-matched controls. DXA and HR-pQCT were used to assess BMD and bone structure. Serum serotonin, sclerostin, dickkopf-related protein 1 (DKK1), and BTM were evaluated. Z-scores for the forearm, total hip, lumbar spine, forearm, and whole body were significantly increased (mean AE SD) between 4.94 AE 1.45 and 7.52 AE 1.99 in cases versus À0.19 AE 1.19 to 0.58 AE 0.84 in controls. Tibial and radial cortical areas, thicknesses, and BMD were significantly higher in cases. In cases, BMD at the lumbar spine and forearm and cortical thickness were positively associated and trabecular area negatively associated with age (r ¼ 0.49, 0.57, 0.74, and À0.61, respectively, p < .05). Serotonin was lowest in cases (69.5 [29.9-110.4] ng/mL versus 119. 4 [62.3-231.0] ng/mL, p < .001) and inversely associated with tibial cortical density (r ¼ À0.49, p < .05) and directly with osteocalcin (OC), bone-specific alkaline phosphatase (B-ALP), and procollagen type 1 amino-terminal propeptide (PINP) (r ¼ 0.52-0.65, p < .05) in controls only. OC and S-CTX were lower and sclerostin higher in cases, whereas B-ALP, PINP, tartrate-resistant acid phosphatase (TRAP), and dickkopf-related protein 1 (DKK1) were similar in cases and controls. In conclusion, increased bone mass in Lrp5-HBM patients seems to be caused primarily by changes in trabecular and cortical bone mass and structure. The phenotype appeared to progress with age, but BTM did not suggest increased bone formation. ß

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Section: J Jbmrmentioning

confidence: 99%

Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high-bone-mass phenotype due to a mutation in Lrp5

Frost

Andersen

Gossiel

et al. 2011

Journal of Bone and Mineral Research

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“…Based on several families with ADO from the county of Funen, Denmark, in the mid-1980s, we described two distinct radiological forms based on plain radiographs (8). Further studies characterizing ADO at the clinical, biochemical, histological, and biomechanical levels revealed that these types corresponded to two distinct disorders, which we designated as ADO type 1 (ADO1) and ADO2 (9,10,11,12,13). These early studies were reviewed in 1989 (14).…”

Section: Introductionmentioning

confidence: 99%

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Bollerslev

Henriksen

Nielsen

et al. 2013

European Journal of Endocrinology

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Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the first propeller of LRP5, a region of importance for binding inhibitory proteins. Thereby, ADO1 cannot be regarded as a classical form of osteopetrosis but must now be considered a disease of LRP5 activation. ADO (Albers-Schönberg disease, or previously ADO2) is characterized by increased number of osteoclasts and a defect in the chloride transport system (ClC-7) of importance for acidification of the resorption lacuna (a form of Chloride Channel 7 Deficiency Osteopetrosis). Ex vivo studies of osteoclasts from ADO have shown that cells do form normally but have reduced resorption capacity and an expanded life span. Bone formation seems normal despite decreased osteoclast function. Uncoupling of formation from resorption makes ADO of interest for new strategies for treatment of osteoporosis. Recent studies have integrated bone metabolism in whole-body energy homeostasis. Patients with ADO may have decreased insulin levels indicating importance beyond bone metabolism. There seems to be a paradigm shift in the treatment of osteoporosis. Targeting ClC-7 might introduce a new principle of dual action. Drugs affecting ClC-7 could be antiresorptive, still allowing ongoing bone formation. Inversely, drugs affecting the inhibitory site of LRP5 might stimulate bone formation and inhibit resorption. Thereby, these studies have highlighted several intriguing treatment possibilities, employing novel modes of action, which could provide benefits to the treatment of osteoporosis.

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“…None of our probands had a history of osteomyelitis, which, especially in the jaw, also traditionally has been associated with autosomal-dominant osteopetrosis (Johnston et al 1968, Beighton et al, 1977. Radiograpy of the long bones has revealed an equally enlarged cortical thickness and a normal total subperiosteal width in the t w o radiographic types of autosomal-dominant osteopetrosis (Bollerslev and Andersen 1988). The distribution of peripheral osteosclerosis in the long bones did not seem to differ between the types.…”

Section: Discussionmentioning

confidence: 91%

“…Fracture complications were also more frequent in Type IT Within the autosomal-dominant form of osteopetrosis, two distinct and strictly family-related radiographic types have recently been described (Andersen and Bollerslev 1987).Themost striking~ndinginTypeIis pronounced sclerosis of the cranial vault (Figure l), whereas"Rugger Jersey Spine" (Figure 2) and endobones (bone within a bone) in the pelvis are characteristic findings in Type 11. Both types show radiographic signs of defective bone resorption (Bollerslev and Andersen 1988). The autosomal-dominant form is often asymptomatic, and the diagnosis may be reached by chance (Johnston et al 1968.…”

Section: Fracture Patterns In Two Types Of Autosomal-dominant Osteopementioning

confidence: 99%

Fracture patterns in two types of autosomal-dominant osteopetrosis

Bollerslev

Andersen

1989

Acta Orthopaedica Scandinavica

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Radiological, biochemical and hereditary evidence of two types of autosomal dominant osteopetrosis

Cited by 171 publications

References 13 publications

Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high-bone-mass phenotype due to a mutation in Lrp5

Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high-bone-mass phenotype due to a mutation in Lrp5

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Fracture patterns in two types of autosomal-dominant osteopetrosis

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