Relevant genetic variants are common in women with pregnancy and lactation-associated osteoporosis (PLO) and predispose to more severe clinical manifestations

Butscheidt, Sebastian; Tsourdi, Elena; Rolvien, Tim; Delsmann, Alena; Stürznickel, Julian; Barvencik, Florian; Jakob, Franz; Hofbauer, Lorenz C.; Mundlos, Stefan; Kornak, Uwe; Seefried, Lothar; Oheim, Ralf

doi:10.1016/j.bone.2021.115911

Cited by 23 publications

(29 citation statements)

References 41 publications

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“…In line with previous studies [ 7 , 8 , 10 , 11 ], the trabecular bone was more affected than the cortical bone but recovered earlier. At 7 months postpartum, aBMD T -score was worse at the lumbar spine (predominantly trabecular) than at the total hip (cortical and trabecular), and trabecular BMD was relatively lower than cortical BMD at the distal radius and tibia.…”

Section: Discussionsupporting

confidence: 92%

“…Additionally, they may experience a decrease in volumetric BMD and changes in bone microarchitecture at the distal tibia and proximal radius [ 8 , 9 ]. In PLO, bone loss is aggravated, and impaired volumetric BMD and bone microarchitecture have been reported compared to healthy controls [ 10 ] and healthy lactating women [ 11 ]. The woman in this report also had a severely impaired aBMD, volumetric BMD, and bone microarchitecture compared to healthy controls, which even after treatment persisted until 40 months postpartum.…”

Section: Discussionmentioning

confidence: 99%

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Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures

et al. 2023

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Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, of which the pathogenesis and best treatment options are unclear. In this report, we describe the case of a 34-year old woman diagnosed with severe osteoporosis and multiple vertebral fractures after her first pregnancy, who was subsequently treated with teriparatide (TPTD) and zoledronic acid (ZA). We describe the clinical features, imaging examination, and genetic analysis. Substantial improvements were observed in areal and volumetric bone mineral density (BMD), microarchitecture, and strength between 7 and 40 months postpartum as assessed by dual-energy X-ray absorptiometry at the total hip and spine and by high-resolution peripheral quantitative CT at the distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA, while at the distal tibiae, physiological recovery and postpartum physiotherapy due to leg pain after stumbling may have played a major role. Additionally, the findings show that, despite the improvements, BMD, microarchitecture, and strength remained severely impaired in comparison with healthy age- and gender-matched controls at 40 months postpartum. Genetic analysis showed no monogenic cause for osteoporosis, and it is suggested that PLO in this woman could have a polygenic origin with possible susceptibility based on familiar occurrence of osteoporosis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures

et al. 2023

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“…Remarkably and unexpectedly, a significant number of individuals presented reduced aBMD values, and one‐half had even developed osteoporosis, in contrast to previous reports. ( 16,20 ) In one case, PLAO unmasked the underlying hereditary bone disorder as shown for other genes, ( 39 ) extending the spectrum of manifestation in individuals with SLC34A3 variants. In that context, a combined deterioration of bone microarchitecture with cortical pronunciation was detected, encompassing the insights of potential bone loss in individuals with SLC34A3 variants.…”

Section: Discussionmentioning

confidence: 94%

Clinical Spectrum of Hereditary Hypophosphatemic Rickets With Hypercalciuria (HHRH)

Stürznickel

Heider

Delsmann

et al. 2020

Journal of Bone and Mineral Research

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Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) represents an FGF23-independent disease caused by biallelic variants in the solute carrier family 34-member 3 (SLC34A3) gene. HHRH is characterized by chronic hypophosphatemia and an increased risk for nephrocalcinosis and rickets/osteomalacia, muscular weakness, and secondary limb deformity. Biochemical changes, but no relevant skeletal changes, have been reported for heterozygous SLC34A3 carriers. Therefore, we assessed the characteristics of individuals with biallelic and monoallelic SLC34A3 variants. In 8 index patients and 5 family members, genetic analysis was performed using a custom gene panel. The skeletal assessment comprised biochemical parameters, areal bone mineral density (aBMD), and bone microarchitecture. Pathogenic SLC34A3 variants were revealed in 7 of 13 individuals (2 homozygous, 5 heterozygous), whereas 3 of 13 carried monoallelic variants of unknown significance. Whereas both homozygous individuals had nephrocalcinosis, only one displayed a skeletal phenotype consistent with HHRH. Reduced to low-normal phosphate levels, decreased tubular reabsorption of phosphate (TRP), and high-normal to elevated values of 1,25-OH 2 -D 3 accompanied by normal cFGF23 levels were revealed independently of mutational status. Interestingly, individuals with nephrocalcinosis showed significantly increased calcium excretion and 1,25-OH 2 -D 3 levels but normal phosphate reabsorption. Furthermore, aBMD Z-score <À2.0 was revealed in 4 of 8 heterozygous carriers, and HR-pQCT analysis showed a moderate decrease in structural parameters. Our findings highlight the clinical relevance also of monoallelic SLC34A3 variants, including their potential skeletal impairment. Calcium excretion and 1,25-OH 2 -D 3 levels, but not TRP, were associated with nephrocalcinosis. Future studies should investigate the effects of distinct SLC34A3 variants and optimize treatment and monitoring regimens to prevent nephrocalcinosis and skeletal deterioration.

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“…It has been suggested that genetic and endocrine factors play an important role in the development of PLO. Mutations in low-density lipoprotein receptor-related protein 5 (LRP5) have been found to be signi cantly associated with PLO [12][13][14]. Low-estrogen status after long-term anorexia, stress, excessive exercise and even premature ovarian failure, have been documented to be correlated with PLO [15].…”

Section: Discussionmentioning

confidence: 99%

Pregnancy- and lactation-associated osteoporosis: A report of six cases

Qian¹,

Wang²,

Qu³

et al. 2023

Preprint

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Objective To illustrate the clinical characteristics of pregnancy- and lactation-associated osteoporosis (PLO) by retrospectively analyzing six cases of PLO. Methods Six cases of PLO diagnosed in our Endocrinology and Orthopedics Departments from January 2018 to June 2020 were retrospectively studied. The baseline characteristics, clinical features, laboratory findings, radiological manifestations and follow-up outcomes were analyzed and compared with previous reports. Results The mean age of the six patients was 33.5 years old (range 30-36 years) with a mean height of 163 cm (range 151-171 cm), mean weight of 56.2 kg (range 47-73 kg) and mean body mass index (BMI) of 21.3 kg/m2 (range 17.4-28.5 kg/m2). All enrolled patients complained of low back pain, with a mean visual analogue scale (VAS) score of 7.0 points (4-10). The mean bone mineral density (BMD), as assessed by the Z-score obtained from the dual-energy X-ray absorptiometry measurement, was -2.90 (range -4.37- -1.34). All six patients underwent magnetic resonance imaging (MRI) scans and vertebral compressive fractures were detected in four patients. The main feature of MRI images of the patients was the appearance of strip-shaped abnormal signal area under the upper endplate of the vertebrae, with low T1 phase signal and high T2 fat-suppressed phase signal. The fractures mainly affected the thoracolumbar regions. Fractures in four patients were all multiple vertebral fractures, with at least two and at most nine vertebral fractures. All six patients received conservative treatment, and no surgical intervention. After a mean follow-up of 27.3 months (range 24-31 months), the symptoms of the six patients were significantly relieved, although four patients still had low back pain to varying degrees. Conclusion PLO tends to occur in older and thinner women with clinical manifestations varying in severity. MRI often reveals multiple vertebral compressive fractures in patients with PLO. PLO has good prognosis with conservative treatment, but complete relief may take a long time.

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Relevant genetic variants are common in women with pregnancy and lactation-associated osteoporosis (PLO) and predispose to more severe clinical manifestations

Cited by 23 publications

References 41 publications

Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures

Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures

Clinical Spectrum of Hereditary Hypophosphatemic Rickets With Hypercalciuria (HHRH)

Pregnancy- and lactation-associated osteoporosis: A report of six cases

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