Effect of declining renal function on bone density in aging women

Buchanan, J.R.; Myers, Cathleen; Greer, Robert B.

doi:10.1007/bf02555161

Cited by 43 publications

(23 citation statements)

References 30 publications

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“…While some studies report decreased circulating levels of 1,25(OH)2D3 with age (42)(43)(44), similar findings were not observed by others (45)(46)(47). Nevertheless, an impaired ability ofthe aging kidneys to convert 25-hydroxyvitamin D3 to 1,25-(OH)2 D3 may contribute to lower circulating levels with age (44,46,48). 1,25-(OH )2 D3 receptor levels in rats and in peripheral blood mononuclear cells of women are reduced with age (49,50).…”

Section: Discussionmentioning

confidence: 54%

Age- and gender-related changes in the distribution of osteocalcin in the extracellular matrix of normal male and female bone. Possible involvement of osteocalcin in bone remodeling.

Ingram¹,

Park²,

Clarke³

et al. 1994

J. Clin. Invest.

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IntroductionWith increasing age, bone undergoes changes in remodeling that ultimately compromise the structural integrity ofthe skeleton. The presence of osteocalcin in bone matrix may alter bone remodeling by promoting osteoclast activity. Whether ageand/or gender-related differences exist in the distribution of osteocalcin within individual bone remodeling units is not known. In this study, we determined the immunohistochemical distribution of osteocalcin in the extracellular matrix of iliac crest bone biopsies obtained from normal male and female volunteers, 20-80 yr old. Normal bone metabolism is the result of a highly integrated relationship between bone resorption and formation. With age, the structural integrity of the skeleton declines along with the functional capacity of various organ systems. Although overall bone mass decreases with age in females and males, the rate of bone loss in females is greater than males ( 1-3). The mechanisms by which bone remodeling is altered with age and gender are poorly understood. The organic phase of normal bone consists of 90% type I collagen and the remaining 10% is composed of noncollagenous proteins (NCPs).' NCPs are synthesized and secreted by bone cells, and their expression is regulated, in part, by local growth factors and hormones (4-7). Accumulating evidence suggests that the extracellular matrix of bone exerts profound effects on cellular activity by retaining NCPs and growth factors that influence both immediate and long-term cell-matrix interactions (8-13). Reduced recruitment of osteoclasts to devitalized particles of bone from human donors of increasing age suggests that bone matrix components may be partially responsible for impaired skeletal remodeling associated with aging (9).Osteocalcin is a 6.5-kD vitamin K-dependent, gamma-carboxyglutamic acid-containing NCP secreted by osteoblasts and odontoblasts. Due to its high affinity for calcium and hydroxyapatite, osteocalcin is incorporated into the extracellular matrix of bone ( 14-16). A growing body of evidence suggests that this matrix protein is involved in bone remodeling. Significant differences in the concentration ofextractable osteocalcin between cortical and trabecular bone in humans provides evidence of distinct regulatory mechanisms among these areas (10). Osteocalcin-deficient bone particles obtained from warfarn-treated rats recruit fewer osteoclasts and are resorbed less than normal particles using in vivo assays ( 1 1, 17, 18). Osteopetrotic rat bone contains low concentrations of osteocalcin, and osteoclast activity in these animals is reduced ( 19).The possibility that NCPs are involved in regulating sitespecific cell-matrix interactions is supported by studies that have immunolocalized NCPs within the extracellular matrix of bone from several species (13,(20)(21)(22). Presently, it is not known whether age or gender differences exist in the microanatomical distribution of NCPs within bone remodeling units. In this study, the immunohistochemical distribution of osteocalcin in ...

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Section: Discussionmentioning

confidence: 54%

Age- and gender-related changes in the distribution of osteocalcin in the extracellular matrix of normal male and female bone. Possible involvement of osteocalcin in bone remodeling.

Ingram¹,

Park²,

Clarke³

et al. 1994

J. Clin. Invest.

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“…Several factors could explain the association between CKD and osteoporosis and osteopenia. Patients with CKD are likely to be older and have lower levels of vitamin D. In addition, there is increasing evidence that CKD itself is a risk factor for low BMD [4][5][6][7]. Patients with impaired renal function have been found to have greater rates of bone loss [7,20].…”

Section: Discussionmentioning

confidence: 99%

“…More than half of individuals older than 70 years have a decreased estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m 2 ) [3]. CKD is an independent risk factor for osteoporosis [4][5][6][7]. Individuals with CKD may have an increased risk for osteoporosis for several reasons, including shared risk factors for both conditions such as advanced age and female gender.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Denosumab for the Treatment of Osteoporosis in Patients with Chronic Kidney Disease

Suzuki¹,

Kihara²,

Mano³

et al. 2017

J Clin Exp Nephrol

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Background: Chronic kidney disease (CKD) is an independent risk factor for osteoporosis and may lead to metabolic abnormalities that accelerate bone loss. Bisphosphonates, the most widely used treatment for osteoporosis, are contraindicated in patients with severe renal impairment. In the present study, we assessed whether denosumab is a safe and effective treatment for osteoporosis in patients with CKD.

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“…[1][2][3][4][5] CKD may have an increased risk for osteoporosis for several reasons, including shared risk factors for both conditions such as advanced age and female gender. Alternatively, CKD may lead to metabolic abnormalities that accelerate bone loss, such as chronic metabolic acidosis, hypogonadism, hyperparathyroidism, and abnormalities with vitamin D metabolism.…”

mentioning

confidence: 99%

The Effect of Raloxifene Treatment in Postmenopausal Women with CKD

Ishani

Blackwell

Jamal

et al. 2008

Journal of the American Society of Nephrology

127

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It is unknown whether treatment for osteoporosis with raloxifene is safe or effective in those with chronic kidney disease (CKD). With data from a multicenter, randomized, placebo-controlled trial of 7705 postmenopausal women with osteoporosis, the effect of raloxifene on rate of change of bone mineral density (BMD), incidence of fractures, and adverse events by stage of CKD was examined over 3 yr. Baseline serum creatinine values were available for 7316 women, and these values were used to assign a category of creatinine clearance (CrCl) using the Cockcroft-Gault formula (CrCl Ͻ45, 45 to 59, and Ն60 ml/min). BMD was measured at baseline and annually by dual x-ray absorptiometry. Within the placebo group, lower baseline CrCl was associated with a trend for higher annual losses of BMD at the femoral neck; however, within the raloxifene group, lower baseline CrCl was associated with greater increases in femoral neck BMD. This interaction between category of CrCl and treatment assignment was significant for rate of change of BMD at the hip. Irrespective of kidney function, raloxifene treatment was associated with a greater increase in spine BMD, a reduction in vertebral fractures, and no effect on nonvertebral fractures compared with placebo. Within each category of kidney function, adverse events were similar between the raloxifene and placebo groups. In conclusion, raloxifene increases BMD at both the hip and the spine and reduces the risk for vertebral fractures among individuals with CKD. The effect of raloxifene on hip BMD is greater among those with mild to moderate CKD.

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Effect of declining renal function on bone density in aging women

Cited by 43 publications

References 30 publications

Age- and gender-related changes in the distribution of osteocalcin in the extracellular matrix of normal male and female bone. Possible involvement of osteocalcin in bone remodeling.

Age- and gender-related changes in the distribution of osteocalcin in the extracellular matrix of normal male and female bone. Possible involvement of osteocalcin in bone remodeling.

Efficacy and Safety of Denosumab for the Treatment of Osteoporosis in Patients with Chronic Kidney Disease

The Effect of Raloxifene Treatment in Postmenopausal Women with CKD

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