Pregnancy and Lactation-Associated Osteoporotic Spinal Fractures: A Case Report

Introduction

Pregnancy and lactation-associated osteoporosis (PLO) is a rare condition (4–8 to 460 cases per million pregnancies or childbirths) typically characterized by vertebral fractures, which occur more frequently during lactation than pregnancy [1–3]. The pathogenesis of PLO may relate to physiological regulation in the mother during pregnancy and lactation: to support fetal and infant development, calcium is mobilized from maternal bone stores for transfer to the child. When the rate of bone calcium loss exceeds the body’s compensatory capacity, osteoporosis may develop. Limited physician recognition of PLO’s clinical manifestations contributes to delayed diagnosis and misdiagnosis. This case report describes a 31-year-old woman who developed lower back pain 2 weeks postpartum and experienced diagnostic delay due to initial misdiagnosis.

Case Report

A 31-year-old Chinese woman (body mass index [BMI] 17.63 kg/m2), an office clerk with a sedentary lifestyle, had no history of tobacco use, alcohol consumption, substance abuse, fractures, oral contraceptive use, or eating disorders; she had not taken vitamin supplements before pregnancy. Two weeks after initiating breastfeeding upon cesarean delivery of her first child, which was conceived naturally, she developed low back pain. The pain intensity was rated 5 on the visual analog scale and worsened with postural changes. The patient delayed seeking medical care because of adherence to the traditional Chinese postpartum confinement custom “Zuo Yue Zi,” which requires new mothers to avoid cold exposure, drafts, and outdoor activity for 1 month after delivery. She endured the pain for 2 weeks before seeking hospital evaluation. Without imaging examination, the clinician attributed her symptoms to epidural anesthesia puncture from the cesarean section. Because she was breastfeeding, analgesics were withheld, and physical therapy was prescribed. However, her pain intensified after 1 week of therapy.

Three weeks after symptom onset, she consulted a general practitioner. Lumbar magnetic resonance imaging revealed multiple vertebral fractures (Figure 1). Subsequent dual-energy X-ray absorptiometry confirmed severe osteoporosis. Laboratory tests showed a 25-hydroxyvitamin D level of 19.94 ng/mL (reference range: >30 ng/mL) and serum calcium level of 2.2 mmol/L (reference range: 2.11–2.52 mmol/L). The general practitioner considered vitamin D deficiency the likely cause of her osteoporosis. Oral calcium and vitamin D (CaD) supplementation did not relieve her symptoms.

Five weeks after symptom onset, evaluation by a spine surgeon ruled out secondary causes of osteoporosis, including hyperparathyroidism (parathyroid hormone: 26.5 pg/mL; reference range: 15–65 pg/mL) and hyperthyroidism (free thyroxine: 15 pmol/L [reference range: 12–22 pmol/L). Spinal infection and lymphoma were also excluded. Because the patient’s symptoms did not improve with vitamin D supplementation and occurred during lactation, a diagnosis of PLO was favored over vitamin D deficiency. Management included discontinuation of breastfeeding, bisphosphonate therapy with zoledronic acid (Aclasta, 5 mg, once yearly), thoraco-lumbo-sacral-orthotic bracing, and continued CaD supplementation. Pain gradually subsided with this regimen and resolved completely by 16 weeks after onset.

At the 19-month follow-up, serum calcium and vitamin D levels were within normal ranges. Lumbar spine bone mineral density (BMD) showed improvement but remained in the severe osteoporosis category; BMD in most hip areas showed no improvement and had declined further (Table 1).

Discussion

PLO is a rare condition, with reported incidence rates ranging from approximately 4 to 8 cases per million pregnancies. However, a Japanese study showed an incidence of 460 cases per million pregnancies, whereas research from the United Kingdom estimated 6.8 cases per 100,000 pregnancies. These substantial differences may reflect variations in ethnicity, lifestyle, and study sample size [1–3]. Due to its rarity and limited clinical awareness – some clinicians may be unfamiliar with the disease – both the initial clinician and the general practitioner in the present case failed to reach an accurate diagnosis.

Vitamin D deficiency represents 1 of several factors contributing to osteoporosis in our patient. The pathogenesis of PLO is not fully understood. The substantial maternal transfer of calcium and phosphorus to the fetus and infant during pregnancy and lactation is considered a primary mechanism. A full-term fetus contains approximately 30 g of calcium, 20 g of phosphorus, and 0.8 g of magnesium; around 80% of these minerals are obtained from the mother during late pregnancy. During the first 6 months of lactation, the infant receives approximately 200 mg of calcium daily through breast milk [4]. The breast, as a key component of the “brain–breast–bone” circuit, functions as a central regulator of bone metabolism during lactation. Suckling and prolactin suppress hypothalamic gonadotropin-releasing hormone, reducing gonadotropin secretion and leading to low levels of ovarian sex hormones, including estradiol and progesterone. The decrease in estrogen upregulates receptor activator of nuclear factor κB ligand (RANKL), which promotes osteoclastogenesis and bone resorption. Enhanced bone resorption, mediated by elevated levels of breast-derived parathyroid hormone-related peptide (PTHrP) in the context of low estrogen, mobilizes calcium from bone into the circulation to support calcium secretion into breast milk [4]. During lactation, calcium transfer from the mother’s skeleton to the infant occurs through the brain–breast–bone axis. Accordingly, discontinuation of breastfeeding has become a widely accepted therapeutic measure for PLO [5–7]. This approach was utilized in the present case. PTHrP serves as an important diagnostic indicator for PLO because it maintains normal maternal serum calcium levels and can occasionally induce hypercalcemia to ensure adequate calcium delivery to the infant. This mechanism may explain the coexistence of vitamin D deficiency with normal serum calcium levels in our patient. Unfortunately, laboratory limitations precluded PTHrP testing in the present case.

Discontinuation of breastfeeding is important but insufficient, particularly in cases involving multiple vertebral fractures [8]. Previous studies have demonstrated that teriparatide is more effective than CaD supplementation alone; both teriparatide and bisphosphonates can increase BMD [9–11]. Zoledronic acid has a longer duration of action than teriparatide, which may affect short-term pregnancy planning. Thus, bisphosphonates are not an optimal choice for patients intending to conceive in the near future [12]. In the present case, the patient had no plans for a second pregnancy. Considering cost-effectiveness and medical insurance coverage, zoledronic acid was selected as the treatment option.

Our patient’s BMI was 17.63 kg/m2, and previous studies have indicated that low BMI may be a risk factor for PLO [1,13]. At the 19-month follow-up, lumbar spine BMD had improved, but BMD in most hip areas had declined. This outcome differs from earlier reports of bisphosphonate and CaD therapy, in which both lumbar and hip BMD increased [14,15]. Low BMI is a potential risk factor for postmenopausal osteoporosis in women. The lack of substantial improvement in BMD – and the observed decrease in hip BMD – despite bisphosphonate and CaD therapy may be attributable to our patient’s low BMI [16,17]. Low BMI might increase the risk of PLO and be associated with reduced responsiveness to bisphosphonate therapy.

Women with low BMI should carefully monitor their bone health during pregnancy and lactation. Future research should include multidisciplinary, multicenter studies with large sample sizes. Compared with X-rays, ultrasound-based bone density assessment may offer a more convenient approach to monitor bone density changes in pregnant and lactating women, although its accuracy requires further validation. Current anti-osteoporotic agents may be effective for treating PLO; however, none are specific to this condition. Given the growing awareness of PLO and advances in research concerning its pathophysiology, more targeted therapeutic options are expected to emerge.

Conclusions

PLO remains underrecognized in clinical practice. Its true incidence may be underestimated due to underdiagnosis and misdiagnosis; no standardized guidelines currently exist for its diagnosis and management. In both diagnosis and treatment, low BMI should be regarded as a potentially important factor. The treatments described in this report – including breastfeeding cessation, CaD supplementation, orthopedic bracing, and administration of anti-osteoporotic medications – may serve as a reference for managing PLO. Multicenter studies are needed to develop evidence-based diagnostic and therapeutic guidelines for this condition.