Reduced Bone Mass in Daughters of Women with Osteoporosis

Seeman, Ego; Hopper, John L.; Bach, Leon A.; Cooper, Mark E.; Parkinson, Elizabeth I.; McKay, John; Jerums, George

doi:10.1056/nejm198903023200903

Cited by 561 publications

(133 citation statements)

References 11 publications

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“…In addition, the studies have shown that the genetic effects on BMD are not constant throughout the skeleton. It was well known that the genetic and environmental contribution to bone mass differed according to skeletal site, as shown by the lower genetic effect on hip BMD than spine BMD, both in twin [8]and mother-daughter [10]models. In accordance, the VDR alleles had a weak effect at the neck of the femur, a predominantly cortical bone site, and a stronger effect at the lumbar spine, a predominantly trabecular bone site.…”

Section: Vitamin D Receptor Genementioning

confidence: 99%

“…Hormones are variables presenting physiologic and pathologic variations, whereas nutrition and exercise may positively or negatively influence the process. The genetic regulation of bone mass acquisition has been known for many years, resulting from studies in families with a high incidence of osteoporosis, in monozygotic (MZ) or dizygotic (DZ) twins, or on inter-racial differences [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17]. Possible candidate genes implicated in such a regulation have been discussed over the last decade and a certain number of associations between candidate gene polymorphisms and variations in BMD have been described [18, 19, 20, 21, 22, 23, 24, 25](table 1).…”

Section: Introductionmentioning

confidence: 99%

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Genetic Determinants of Bone Mass

Audı́¹,

Garcia-Ramírez²,

Carrascosa³

1999

Horm Res Paediatr

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A genetic contribution to bone mass determination was first described in the early 70s. Elucidation of gene contribution to this has since been attempted through studies analyzing associations between bone mass acquisition and/or maintenance and polymorphic variations of several genes. The first to be described was the vitamin D receptor gene (VDR), initially claimed to contribute to almost 75% of the genetic variation in bone mineral density (BMD) in twin and general population studies. Not all of the studies published to date conclude that a clear relationship exists between polymorphic VDR alleles and BMD, and the molecular basis for the VDR gene polymorphisms influence on bone mineralization has not yet been clarified. Since then, other genes with a significant role in bone metabolism such as estradiol receptor, collagen type 1_α1, TGF-β₁, interleukin-6, calcitonin receptor, α₂-HS-glycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, β₃-adrenergic receptor, apolipoprotein E, PTH, IGF-I and glucocorticoid receptor have been analyzed. Some polymorphic variations in these genes have been associated in some works with significant differences in BMD, with even more significant contributions when associations of different gene polymorphisms were analyzed. Again, the molecular basis for the contribution of these alleles to bone mass determination has not yet been described. A different approach has been attempted by linkage analysis of loci involved in bone density in pedigrees with low BMD using BMD as a quantitative trait. Recent results do not confirm, in these families, any association with any of the previously reported genes, but rather with other as yet unidentified genes. The genetic contribution to mild variations in the general population, as a result of environmental and endogenous individual influences, probably differs completely from that providing a pathologic BMD.

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Section: Vitamin D Receptor Genementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic Determinants of Bone Mass

Audı́¹,

Garcia-Ramírez²,

Carrascosa³

1999

Horm Res Paediatr

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“…Type I osteoporosis is apparently triggered by the transient acceleration of bone loss that occurs with the fall in estrogen levels in women at menopause. Several reports suggest that the disease is familial (1,2,4).…”

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confidence: 99%

Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta.

Spotila

Constantinou

Sereda

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

130

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Mutations in the two genes for type I collagen (COLIAJ or COLIA2) cause osteogenesis imperfecta (01), a heritable disease characterized by moderate to extreme brittleness of bone early in life. Here we show that a 52-year-old postmenopausal woman with severe osteopenia and a compression fracture of a thoracic vertebra had a mutation in the gene for the a2(I) chain of type I collagen (COLIA2) similar to mutations that cause 01. cDNA was prepared from the woman's skin fibroblast RNA and assayed for the presence of a mutation by treating DNA heteroduplexes with carbodiimide. The results indicated a sequence variation in the region encoding amino acid residues 660-667 of the a2(1) chain. Further analysis demonstrated a single-base mutation that caused a serine-for-glycine substitution at position 661 of the a2(I) triple-helical domain. The substitution produced posttranslational overmodification of the collagen triple helix, as is seen with most glycine substitutions that cause O0. The patient had a history of five previous fractures, slightly blue sclerae, and slight hearing loss. Therefore, the results suggest that there may be phenotypic and genotypic overlap between mild osteogenesis imperfecta and postmenopausal osteoporosis, and that a subset of women with postmenopausal osteoporosis may have mutations in the genes for type I procollagen.Involutional osteoporosis (1, 2) is a severe health problem that causes over 1.2 million fractures per year in the United States (1). Two forms of the disease have been described: postmenopausal or type I osteoporosis that primarily affects women within 15 to 20 years after menopause, and agerelated or type II osteoporosis that occurs in both men and women over the age of 70. From 15% to 20% of women develop vertebral fractures from postmenopausal osteoporosis, and more than half of women over the age of 70 years have fractures related to osteoporosis (1, 3). Both types of osteoporosis are probably determined, in part, by insufficient accumulation of skeletal mass in young adulthood (1, 2). Normally, bone mass increases until age 30 and then declines. When bone density drops below a threshold level, fractures occur following minor trauma. Type I osteoporosis is apparently triggered by the transient acceleration of bone loss that occurs with the fall in estrogen levels in women at menopause. Several reports suggest that the disease is familial (1, 2, 4).The bone fragility of osteoporosis resembles that seen in mild forms of osteogenesis imperfecta (01), a heritable disease characterized by brittleness of bone early in life (5-7). In 01 the decrease in bone mass and the consequent bone fragility vary from mild to severe. The most severe variants of 01 are lethal, but many are milder. Some probands with milder variants have multiple fractures as children, are relatively fracture-free for many years after puberty, but then experience increased numbers of fractures later in life. The increase in fractures can be particularly prominent in women following menopause. Mild 01 i...

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“…As bone loss is associated with aging, investigators have reasoned that people who have fractures and low bone density probably have lost more bone mass than people who do not have fractures [11,12,13]. This hypothesis may be correct, but an alternative explanation may be true as well: people with fractures may have achieved a lower peak bone mass as young adults and subsequently lost bone mass at the same rate as the rest of the population [14]. …”

Section: Introductionmentioning

confidence: 99%

Factors Predisposing to Osteoporosis in Childhood: New Concepts in Diagnostics

Schöenau¹,

Fricke²

2007

Horm Res Paediatr

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Background: Bone densitometric data are often difficult to interpret in children and adolescents because of large inter- and intraindividual variations in bone size. We propose a functional approach to bone densitometry that addresses two questions: is bone strength normally adapted to the largest physiological loads represented by muscle force, and is muscle force adequate for body size? Methods and Results: The theoretical background for this approach is provided by the mechanostat theory, which proposes that bones adapt their strength to keep the strain caused by physiological loads close to a set point. Because the largest physiological loads are caused by muscle contractions, there should be a close relationship between bone strength and muscle force or size. The proposed two-step diagnostic algorithm requires a measure of muscle force or size and a measure of bone mineral content at a corresponding location. Conclusion: This approach justifies the hope that more detailed insights into this matter could help devise targeted strategies for the prevention and treatment of pediatric bone diseases.

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Reduced Bone Mass in Daughters of Women with Osteoporosis

Cited by 561 publications

References 11 publications

Genetic Determinants of Bone Mass

Genetic Determinants of Bone Mass

Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta.

Factors Predisposing to Osteoporosis in Childhood: New Concepts in Diagnostics

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