Idiopathic osteoporosis during pregnancy

Clinical rheumatology, 1994, 13, N ° 2

299-304

Case Report

Idiopathic Osteoporosis during Pregnancy O.L. RILLO,

C.A. DI STEFANO,

J. B E R M U D E Z ,

J.A.MALDONADO

COCCO

Summary

Among the idiopathic forms of osteoporosis, the one developing during pregnancy is the least common and scarcely studied. Poorly understood, it seems to stem from transient failure of calcitropic hormones and decreased osteoblast activity. A 25-year-old patient presented with coxofemoral pain during the last three months of pregnancy, followed by multiple vertebral compression fractures at postpartum. Laboratory, radiological, densitometric and histological examinations led to a diagnosis of idiopathic osteoporosis in pregnancy, once other causes of osteopenia had been ruled out. Bone densitometries performed 12 and 24 months later showed an increase in mineral density, thus demonstrating the self:limited nature of this entity.

KO' words

Osteoporosis, Idiopathic Osteoporosis, Pregnancy, Transient

Osteoporosis.

INTRODUCTION Osteoporosis associated with pregnancy and lactation is an infrequent form of idiopathic osteopathy. Its rarity would thus explain why few authors have dealt with the subject since it was first described by B. Nordin in 1955 (1); however, it represents a severe affliction in the tiny group of affected patients. While the most common symptom appears to be axial pain due to vertebral compression (2-7), its relationship with transient osteoporosis of the hip (TOH) remains controversial (8). Its occurrence is neglected since roughly 50% of pregnant women, above all during the last three months, experience some degree of lumbosacral pain, which presents severely ha 15% of cases. Such symptoms during pregnancy are mostly attributed to a combination of mechanical factors including lumbar hyperlordosis and hormone-induced ligament changes leading to mobility in pelvic synarthroses (9-12). We describe here a new case of idiopathic osteoporosis in pregnancy (IOP), followed up by our team for 28 months. By excluding diverse causes of osteopenia, diagnosis was made on the basis of biochemical and radiological examination, as well as bone densitometry by

From the Rheumatologyand Orthopedic SurgeryDepartments, Hospital Privado "24 de Septiembre" and RheumatologySection, Instituto de Rehabilitaci6n Psicofisica, Buenos Aires, Argentina.

dual energy X-ray absorptiometry (DEXA) and bone biopsy. CASE R E P O R T This 25-year-01d patient developed dorsal kyphosis and dorso-lumbar column pain after bearing twins. During the second month of pregnancy she had presented metrorrhagia with the risk of abortion and was kept at complete bed rest for a month, receiving isoxsuprine-progesterone during two months. In the course of the last three months, left inguinal pain appeared, radiating to the internal aspect of the ipsilateral thigh, which increased on walking, forcing her to limp and resort to a walkingstick. Symptomatically treated with analgesics, the pain persisted for about two months, gradually disappearing thereafter. At the end of her pregnancy she was asymptomatic and had gained 12 kg in weight, from an initial weight of 60 kg. Due to maternal dystocia, a Caesarean delivery was performed and two normal girls were born, each weighing 3 kg. Three weeks later, after slight physical effort, she presented with acute pain in the dorso- lumbar column which prevented her from getting about freely and hindered certain activities, including lactation. The pain abated slowly, and disappeared within two months. The patient's gyneco-obstetric history showed that her menses started at age 11 and her cycles were 4/30 days. She had never employed hormonal anticon-

300

O.L. Rillo, C.A. Di St6fano, J. Bermiidez, J.A. Maldonado Cocco

Fig. 1 : Periacetabular osteopenia in left hip.

ceptives. In 1989 she experienced a spontaneous abortion at 2 months' pregnancy, when the anatomo-pathological report indicated involutive placentary remnants. Her family history was likewise unremarkable. Diet was normal before and during pregnancy, with an estimated calcium intake of 1200 mg/day. She denied tobacco or alcohol addiction. At the time of physical examination she was in good general condition. Her weight was 57 kg and her height 1.53 m, after having experienced a loss of 3 cm. She presented dorsal kyphosis and pain on dorso-lumbar percussion. The remainder of the physical examination was normal. There was no evidence of osteogenesis imperrecta, c~shingoid habit or pretibial myxedema. Thyroid, skin, hair and nail examination was likewise nor-

compatible with osteoporosis findings, while histomorphometry showed a 17% formation surface and a 3.2% reabsorption surface (normal values: 19.3 - 4.2 and 3.9 __. 0.6, respectively) (3). The patient was put on 1.5 g/day of calcium supplement and periodic control was initiated. To date, 28 months postpartum, she remains asymptomatic in good health status. Bone densitometry, carried out 12 and 24 months later, disclosed increase in lumbar mineral density, lumbar, fem0r~l neck and whole body values (Table I). In Table II fresh normal laboratory tests may be compared with those made 12 and 26 months earlier.

mal.

Laboratory tests together with pelvis, dorso-lumbar column and peripheral skeleton X-rays were then performed. Relevant findings included alkaline phosphatase 65 mlU/ml (normal value: 21-58) and osteocalcin 3.6 mg/ml (normal value : 3.5-8), as well as pelvian, left acetabulum and femoral head and dorso-lumbar column osteopenia, with shape and height alteration in several vertebral bodies (Figs. 1 and 2). Bone densitometry by DEXA (Lunar DPX-L) in femoral neck, lumbar column and whole body disclosed 0.636 g/cm2, 0.719 g/cm2 and 0.945 g/cm 2 mineral density, with a 33%, 40% and 13% drop, respectively, as compared to normal age-matched controls. The anatomicopathological report on an iliac crest biopsy was

Table I: Values of bone densitometry Initial

L2-L4 (g/cm2)

Basal

0.719

Femoral neck (g/cm2)

Whole body (g/cm2)

0.636 0.945 12 Months

0.821

24 Months

0.912

0.650 0.930 0,720 0.979

% Age matched 60 67 87 68 68 85 76 76 90

Idiopathic osteoporosis during pregnancy

Fig. 2: Lumbar column with biconcave deformity of the superior and inferior surfaces of several vertebral bodies.

301

302

O.L. Rillo, C.A. Di St6fano, J. Bermfidez, J.A. Maldonado Cocco

Table II: Metabolic,phosphocalcium

and hormonal determinations in a patient with idiopathic osteoporosis in pregnancy at immediate and late

posqJartum

Determinations

Calcium

Phosphorus Creatinine Proteinogram

Seric (rag%) Ionic (rag%) Urinary (mg/24h) Seric (rag%) Urinary (g/24h) Seric (rag%) Urinary (g/24h) Seric (g%)

Albumin ett ct2 f5 gamma

Urinary (g/l) SGPT (U/L) SGOT (U/L) Alkaline phosp!aatase (mlU/ml) PTH (RIA pmol/D Urinary OH proline (Procop-Udenfried rag/24 h) TSH (RIA U/ml) T3 (RIA ng%) T4 (RIA g%) FSH (RIA mlU/ml) LH (RIA mIU/ml) Estradiol (RIA pg/ml) Progesterone (:RIA ng/m[) Plasma cortisol (RIA g%) 25 OH VitaminD (Protein component ng/ml) Osteocalcin (RIA nggml)

DISCUSSION The few studies evaluating the factors involved in phosphorus and Calcium metabolism during pregnancy have rendered contradictory results (13-15). Current reports mention that 1-25 OH vitamin D levels are raised during gestation, whereas parathormone (PTH) and osteocalcin values are low at the start of pregnancy and increase towards its end. At six months postpartum, osteocalcin is at higher levels than at three days, which shows that in late puerperittm there would be increased bone turnover (16). Gestation and lactation exert a great calcium demand in order to allow calcification and development of fetal bones and to level off maternal losses. Normally, there is a, 6-8% loss of total body calcium content, some 30 g during pregnancy and another 30 g durhag lactation (!7). It is not unreasonable to assume that this calcium need should be even greater in a twin pregnancy such as the case here presented. Regulatory mech-

February '91 Value (normal value)

April '92 Value

April '93 Value

10.5 (8.5q0.5) 4.5 (4.25-5.25) 148 (100-300) K8 (2.5-4.5) 0.78 (up to 1) 1 (0.7-1.5) 1.4 (1.2-1.7) 4.10 0;20 0.76 0.74 1.20

9.4

8.8

165 2.7 0.60 1 1.3 4.20 0.20 0.68 0.80 1:32

150 3.2 0.6 0.8 0.75 3.80 0.22 0,63 0.86 1.19

8 (4-20) 4 (2-t8) 65 (21:58) 48 (up to 95) 34 (15-65)

4 3 47 20 17

7 7 49 65 26

1.6 (up to 5) 102 (75-190) 7.2 (4.6-12.2) 5.t (5-20) 5 (5-20) 184 (90-200) 11.4 (2.5-28) 13.2 (5-25) 17.6 (t2-24) 3.6 (3.5-8)

1.8 120 6 5.7 7 t94 14.2 11.1 24.1 5

t.8 140 7 10.5 6 170 12 11 23 5

anisms protect the mother from this excessive reabsorption and avoid irreversible changes in bone mass. In our patient, having excluded diverse etiologies of osteopenia, IOP was diagnosed. The clinical picture and the studies performed agree with published cases. Physical examination, absence of familial history, nor~nal laboratory tests, radiology findings and bone histology taken jointly, rule out the possibility of osteogenesis imperfecta, juvenile osteoporosis Orosteomalacia. As previous X-ray examinations were unavailable and no studies had been carried out Off phosphocalcium metabolism during pregnancy, it is Unknown whether the latter initiated or aggravated th e !0sSOf bone mass. However, aggravation seems unlikely since clinical history discloses no evidence raisingsuspid0ns Of underlying bone disease. Complete bed rest at the start of pregnancy should thus be borne in mind. Immobilization activates osteodasts and depresses osteoblastic stimuli, leading to a reduction in bone mass, particularly of the trabecular variety. Monthly losses of mineral content have been

Idiopathic osteoporosis during pregnancy

reported to range from 0.9 to 8% in young adults, after three to six weeks of immobilization (18,19). Although in our :patient a month of bed rest may have been a contributory factor, it fails to explain per se such a marked loss in cortical and trabecular bone as demonstrated by densitometry. Furthermore, it is not unlikely that this generalized bone mass loss initiated as a left T O H . Quite recently, during prospective evaluation of mineral density changes during pregnancy, the loss of 10% bone mass in the femoral neck has been reported as an isolated and hitherto unexplained finding (20). In support, T O H would explain in our patient the features of severe left hip pain during the 5th month of pregnancy. Despite the fact that it is difficult at times to distinguish coxofemoral pain from that arising from lumbar involvement, the gradual disappearance of hip symptoms and the radiological findings in the left hip, in these cases are consistent with such a diagnosis (6,8). Given the possible relationship between T O H and IOP in the pregnant woman, such entities should be regarded as processes having a similar aetiopathogenesis. IOP would therefore prove a pathological process attributable to failure in calcium homeostasis during gestation, triggered by transient insufficiency of calciotropic hormones. The possibility of low calcittrn intake, a low level of 1.25 (OH)2 vitamin D and/or a relative deficiency of calcitonine should be considered in cases of lOP. Improvements in symptoms and in densitometric values, as described in several publications, further confirm the presence of a self-limiting process (1,2,4,6,7). It may be speculated that the placenta as an endocrine organ, on exerting an influence of phosphocalcium metabolism, may well play some role in the pathogenesis of IOP and should be the subject of deeper research. Interestingly, PTH-like substances have been isolated from the placenta of diverse species, including the human one, as well as its capability of inducing hypercalcaemia in the fetus with respect to the mother (21,22).

303

Furthermore, a parathyroid hormone-related peptide (PTHrP) produced in the lactating breast (23) and secreted in high concentrations in the maternal milk (24) has recently been identified. There is now evidence for its release into the circulation of both goats and rats during lactation (25,26). The importance of weaning in the management of women with IOP and possible aetiologicat role for P T H r P were discussed in Reid's case report (27). Although not demonstrated in our patient, histomorphometric studies carried out in l O P cases suggest broadly that there is scarce cellular activity and that it is not due to greater bone reabsorption (3,4). Furthermore, the hypothesis of insufficient bone formation is strengthened by the finding of low threshold osteocalcin levels during late puerperium, as already stated (6). The same findings were true in our patient. Several authors mention the possibility of spontaneous improvement. However, calcium supplements combined with other antiosteoporotic agents have been employed. As a rule, it is advisable to discontinue lactation and keep the patient as active as possible. Future pregnancies are not necessarily contraindicated. These patients should, however, be cautiously- followed during subsequent pregnancies (1-6). It may be concluded that a diagnosis of IOP should be entertained_ when there is severe lumbar pain during pregnancy, above all in the last three months. Quite possibly, sensitive methods with low radiation exposure would prove useful to evaluate bone mass in highly selected cases, in order to reach a firm diagnosis without undue delay and thus avoid complications.

Acknowledgements: The authors thank Dr. Eduardo Santini Araujo, (Seat of Pathology of the School of Dentistry, Universidad de Buenos Aires) for performing histomorphometric studies of bone biopsy, and Ms. Mdnica Sfinchez for secretarial assistance.

REFERENCES

t. Nordin, B.E.C., Roper, A. Post-pregnancyosteoporosis. A syndrome ? Lancet 1955, 1, 431-434. 2. Dent, C., Friedman, M. Pregnancy and idiopathic osteoporosis. Q. 1. Med. 1965, 34, 341-357. 3. Gruber, H.E., Gutteridge, D.H., Baylink, D.J. Osteoporosis associated with pregnancy and lactation : bone biopsy and skeletal features ,in three patients. Metab Bone Dis Ret Res 1984, 5, 159165. 4. Smith, R., Winearls, C.G., Stevenson, J.C., Woods, C.G., Wordworth, B.P. Osteoporosis of pregnancy. Lancet 1985, 1, 11781180. 5. Sonne,M.W. Osteoporosisand pregnancy.JAMA 1986, 255, 2495.

6. Figueroa, M., Belzunegui,J., Paniagua, I., L6pez de Goicoechea, AJ., Gonz~ilez,C. Osteoporosis asociada al embarazo. Rev Esp Reumatol 1990, 17. 201-202. 7. Blanch,J., Chines, A., Pacifi, R. Pregnantlyassociated osteoporosis. Report of two cases with long-term bone density follow-up.J Bone Miner Res 1991, $165 (Abstract). 8. Vinceneux, Ph., Stevens-Dudragne, D., Peckels, B., Kaplan, G. Algodystrophiedecalcifiantede la hanche au cours de la grossesse. Apropos de trois observations. Sere ttop Paris 1979, 55, 17011704. 9. Mantle, M., Greenwood, R., Currey, H. Backache in pregnancy. Rheumatol Rehabil 1977, 16, 95-101.

304

O.L. Rillo, C.A. Di Stdfano, J. Bermfidez, J.A. Maldonado Cocco

10. Le Ban, M., Perrin, J., Latimer, F. Pregnancy and the herniated lumbar disc. Arch Phys Med Rehabil 1983, 64, 319-321. 11. Kelsey, J., Greenberg, R., Hardy, R., Johnson, M. Pregnancy and the syndrome of herniated lumbar intervertebral disc : an epidemiological study. Yale J Biol Med 1975, 48, 361-368. 12. Bishop, E., Cefale, R. The musculoskeletal system, tn : Signs and Symptoms in Disorders of Pregnancy. Ed.: Hagerstown, Lippincott, 1983, 77-81. 13. HiUman, L., Sateesha, S., Hanssler, M., et al. Control of mineral homeostasis during lactation : interrelationships of 25-hydroxyvitamin D, 24-25 dihydroxyvitamin D, 1-25 dihydroxyvitamin D, parathyroid hormone, calcitonin, prolactin and estradiol. Am J Obstet Gynecol 1981, 139, 47t-476. 14. Pitkin, R., Reynolds, W., Williams, G., Hargis, G. Calcium metabolism in normal pregnancy : a longitudinal study. Am J J Obstet Gyneeot 1979, I33, 781-790. 15. Pitkin, R. Calcium metabolism in pregnancy and the perinatat period: a review. Am I Obstet Gynecot 1985, t51, 99-109. 16. Seki, K., Makimura, N., Mitsui, C.,Hirata, J., Nagata, I. Am J Obstet Gynecol 1991, 164, 1248-1252. 17. Fourman, P,, Royer, P. Calcium Metabolism and the Bone. 2rid ed. BlackweU, Western Printing Service Ltd. Bristol 1968, p. 62. 18. Hansson, T , Roos, B., Nachemson, A. Development of osteopenia in fourth lumbar vertebra during prolonged bed rest after operation for scoliosis. Aeta Orthop Scand t975, 46, 621-630. 19. Krolner, B., Tort, B. Vertebral bone loss: an unheeded side effect of therapeutic bed rest. ClJn Sei 1983, 64, 537-540. 20. Sowers, M., Crutchfield, M., Jannausch, M., Updike, S., Corton, G. Prospective evaluation of bone mineral change in pregnancy. Obstet Gynecol 1991, 77, 841-845. 21. Rodda~ Ci, Kubota, M., Heath, J., et al. Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid

22.

23, 24. 25. 26.

27.

glands and sheep placenta : comparisons with a similar protein implicated in humoral hyperealcaemia of malignancy. J Endocr 1988, 117, 261-271. Abbas, S., Pickard, D., Illingworth, D., et al. Measurement of parathyroid hormone-related protein in extracts of fetal parathyroid glands and placental membranes. J Endocr 1990, 124, 319325. Thiede, M., Rodan, G. Expression of calcium-mobilizingparathyroid hormone-like peptide in lactating mammary tissue. Science 1988, 242, 278-280. Budayr, A., Halloran, B., King, J., et al. High levels of parathyroid hormone-like protein in milk. Proc Nat Acad Sci, USA 1989, 86, 7183-7185. Rateliffe, W,, Thompson, G., Care, A., Peaker, M. Production of PTH-retated protein (PTHrP) by mammary gland of the goat. J Endocr 1991, 129 (Abstract 134). Yamamoto, M., Duong, L., Fisher, J., et al. Suckling-mediated increases in urinary phosphate and 3'-5'-cyclic adenosine monophosphate excretion in lactating rats : possible systemic effects of parathyroid hormone-related protein. Endocrinology 1991, 129, 2614-2622. Reid, I., Wattle, D., Evans, M., Budayr, A. Post-pregnancy osteoporosis associated with hypercalcaemia. Clin Endocrinol 1992, 37, 298-303,

Received: 30 March 1993 Revision-accepted: 4 October 1993 Correspondence to: O.L. RILLO, M.D., Secci6n Reumatologia, Instituto de Rehabilitacidn Psicofisica Echeverria 955, t428-Buenos Aires, Argentina.