Women With Pregnancy and Lactation-Associated Osteoporosis (PLO) Have Low Bone Remodeling Rates at the Tissue Level

Adi Cohen, Mafo Kamanda-Kosseh, David W. Dempster, Hua Zhou, Ralph Müller, Elliott Goff, Ivelisse Colon, Mariana Bucovsky, Julie Stubby, Thomas L. Nickolas, Emily M. Stein, Robert R. Recker, Joan M. Lappe, Elizabeth Shane

Research output: Contribution to journalArticle

Abstract

Pregnancy and lactation-associated osteoporosis (PLO) is a rare, severe, early form of osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of idiopathic osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low-trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non-PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue-level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2 /mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications.

Original languageEnglish (US)
Pages (from-to)1552-1561
Number of pages10
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume34
Issue number9
DOIs
StatePublished - Sep 1 2019
Externally publishedYes

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Bone Remodeling
Lactation
Osteoporosis
Pregnancy
Postpartum Period
Bone and Bones
Menstruation

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Women With Pregnancy and Lactation-Associated Osteoporosis (PLO) Have Low Bone Remodeling Rates at the Tissue Level. / Cohen, Adi; Kamanda-Kosseh, Mafo; Dempster, David W.; Zhou, Hua; Müller, Ralph; Goff, Elliott; Colon, Ivelisse; Bucovsky, Mariana; Stubby, Julie; Nickolas, Thomas L.; Stein, Emily M.; Recker, Robert R.; Lappe, Joan M.; Shane, Elizabeth.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 34, No. 9, 01.09.2019, p. 1552-1561.

Research output: Contribution to journalArticle

Cohen, Adi ; Kamanda-Kosseh, Mafo ; Dempster, David W. ; Zhou, Hua ; Müller, Ralph ; Goff, Elliott ; Colon, Ivelisse ; Bucovsky, Mariana ; Stubby, Julie ; Nickolas, Thomas L. ; Stein, Emily M. ; Recker, Robert R. ; Lappe, Joan M. ; Shane, Elizabeth. / Women With Pregnancy and Lactation-Associated Osteoporosis (PLO) Have Low Bone Remodeling Rates at the Tissue Level. In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2019 ; Vol. 34, No. 9. pp. 1552-1561.
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AU - Zhou, Hua

AU - Müller, Ralph

AU - Goff, Elliott

AU - Colon, Ivelisse

AU - Bucovsky, Mariana

AU - Stubby, Julie

AU - Nickolas, Thomas L.

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AU - Shane, Elizabeth

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N2 - Pregnancy and lactation-associated osteoporosis (PLO) is a rare, severe, early form of osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of idiopathic osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low-trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non-PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue-level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2 /mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications.

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